Metformin improves performance in high‐intensity exercise,but not anaerobic capacity in healthy male subjects

The aim of this study was to determine the ergogenic effects of metformin in high‐intensity exercise, as well as its effects on anaerobic capacity, in healthy and physically active men. Ten subjects (mean (± standard deviation) maximal oxygen uptake (_2max) 38.6 ± 4.5 mL/kg per min) performed the following tests in a cycle ergometer: (i) an incremental test; (ii) six submaximal constant workload tests at 40%–90% (_2max); and (iii) two supramaximal tests (110% (_2max). Metformin (500 mg) or placebo was ingested 60 min before the supramaximal test. There were no significant differences between the placebo and metformin groups in terms of maximum accumulated oxygen deficit (2.8 ± 0.6 vs 3.0 ± 0.8 L, respectively; P = 0.08), lactate concentrations (7.8 ± 2.6 vs 7.5 ± 3.0 mmol/L, respectively; P = 0.75) or O₂ consumed in either the last 30 s of exercise (40.4 ± 4.4 vs 39.9 ± 4.0 mL/kg per min, respectively; P = 0.35) or the first 110 s of exercise (29.0 ± 2.5 vs 29.5 ± 3.0 mL/kg per min, respectively; P = 0.42). Time to exhaustion was significantly higher after metformin than placebo ingestion (191 ± 33 vs 167 ± 32 s, respectively; P = 0.001). The fast component of recovery was higher in the metformin than placebo group (12.71 vs 12.18 mL/kg per min, respectively; P = 0.025). Metformin improved performance and anaerobic alactic contribution during high‐intensity exercise, but had no effect on overall anaerobic capacity in healthy subjects.     

Proof-of-concept study on the suitability of 13C-urea as a marker substance for assessment of in vivo behaviour of oral colon-targeted dosage forms

Background and purpose:

¹³C-urea may be a suitable marker to assess the in vivo fate of colon-targeted dosage forms given by mouth. We postulated that release in the colon (urease-rich segment) of ¹³C-urea from colon-targeted capsules would lead to fermentation of ¹³C-urea by bacterial ureases into ¹³CO₂. Subsequent absorption into the blood and circulation would lead to detectable ¹³C (as ¹³CO₂) in breath. If, however, release of ¹³C-urea occurred in the small intestine (urease-poor segment), we expected detectable ¹³C (as ¹³C-urea) in blood but no breath ¹³C (as ¹³CO₂). The differential kinetics of ¹³C-urea could thus potentially describe both release kinetics and indicate the gastrointestinal segment of release.

Experimental approach:

The in vivo study consisted of three experiments, during which the same group of four volunteers participated.

Key results:

The kinetic model was internally valid. The appearance of ¹³C-in breath CO₂ (F_fermented) and the appearance of ¹³C in blood as ¹³C-urea (F_{not fermented}) show a high inverse correlation (Pearson''s r=−0.981, P= 0.06). The total recovery of ¹³C (F_fermented+F_{not fermented}) averaged 99%, indicating complete recovery of the administered ¹³C via breath and blood. ¹³CO₂ exhalation was observed in all subjects. This indicates that ¹³C-urea was available in urease-rich segments, such as the caecum or colon.

Conclusions and implications:

In this proof-of-concept study, ¹³C-urea was able to provide information on both the release kinetics of a colon-targeted oral dosage form and the gastrointestinal segment where it was released.     

Ultrasound as visual feedback in speech habilitation: exploring consultative use in rural British Columbia, Canada

Ultrasound has shown promise as a visual feedback tool in speech therapy. Rural clients, however, often have minimal access to new technologies. The purpose of the current study was to evaluate consultative treatment using ultrasound in rural communities. Two speech-language pathologists (SLPs) trained in ultrasound use provided consultation with ultrasound in rural British Columbia to 13 school-aged children with residual speech impairments. Local SLPs provided treatment without ultrasound before and after the consultation. Speech samples were transcribed phonetically by independent trained listeners. Eleven children showed greater gains in production of the principal target /[image omitted]/ after the ultrasound consultation. Four of the seven participants who received more consultation time with ultrasound showed greatest improvement. Individual client factors also affected outcomes. The current study was a quasi-experimental clinic-based study. Larger, controlled experimental studies are needed to provide ultimate evaluation of the consultative use of ultrasound in speech therapy.     

Reducing alcohol-related damage in populations: rethinking the roles of education and persuasion interventions

AIM: In order to potentially enhance the impact of most effective policies and interventions in reducing the population level damage from alcohol, a new perspective with regard to education and persuasion interventions is offered. METHODS: Recent studies were examined on the global burden of alcohol and also those focusing on the links between overall consumption and high-risk drinking, on one hand, and drinking-related damage on the other hand. A synopsis of main findings from reviews and other analysis provides the basis for conclusions about the impacts of education and persuasion interventions. RESULTS: There is a relative absence of evidence of the effectiveness of education and persuasion in reducing consumption, curtailing high-risk drinking or reducing damage from alcohol. This is in contrast to the rising levels of damage from alcohol, and also to the demonstrated effectiveness of certain alcohol policies and interventions, as summarized in Babor et al. CONCLUSIONS: Given that only a small fraction of education and persuasion interventions have any positive impact, generating 'more of the same' is not an impact-effective and cost-efficient approach. Therefore, interventions that have not been shown to be effective need to be phased out and those most effective and of widest scope should receive more attention and enhanced resources. A reframing of the roles and foci of persuasion interventions is advised, including, for example, focusing on informing policy-makers, and stimulating public discussions about the rationale of alcohol policies and the roles that citizens can play in promoting and supporting these policies.     

Reducing alcohol problems through community action research projects: contexts, strategies, implications, and challenges

Community-based action research projects may include a number of challenges. The secular context may impede a project; for example, reducing aggregate rates of drinking-related problems may involve curtailing very popular high-risk drinking occasions. These projects may also embrace important but unrealistic goals, require matching competing goals emerging from multifoci project teams, or involve convoluted funding arrangements. Attention to team development, priority setting, and project design and evaluation issues is essential. Many projects downplay conceptual issues, such as understanding the nature of communities, organizations, systems, their operation, and social change and prevention models. Focus populations, community members and leaders, change agents team members, funding agencies, and policymakers can benefit from these projects.     

Hereditary coproporphyria and epilepsy

A 9-year-old boy with mental deterioration and epilepsy suffered an acute attack of hereditary coproporphyria associated with worsening of seizure control. Leucocyte coproporphyrinogen oxidase activity was undetectable in the patient during this attack, and was reduced in his mother, a latent case. The complex relationship between porphyria, epilepsy, and anticonvulsant drugs is discussed.     

Encapsulation of plasmid DNA in stabilized plasmid-lipid particles composed of different cationic lipid concentration for optimal transfection activity

In previous work (Wheeler et al. (1999) Gene Therapy 6, 271-281) we have shown that plasmid DNA can be entrapped in "stabilized plasmid lipid particles" (SPLP) using low levels (5-10 mol%) of cationic lipid, the fusogenic lipid dioleoylphosphatidylethanolamine (DOPE), and a polyethyleneglycol (PEG) coating for stabilization. The PEG moieties are attached to a ceramide anchor containing an arachidoyl acyl group (PEG-CerC20). However, these SPLP exhibit low transfection potencies in vitro as compared to plasmid/cationic lipid complexes formed with liposomes composed of cationic and neutral lipid at a 1:1 lipid ratio. The objective of this study was to construct SPLPs with increased cationic lipid contents that result in maximum transfection levels. A phosphate buffer detergent dialysis technique is described resulting in formation of SPLP containing 7-42.5 mol% DODAC with reproducible encapsulation efficiency of up to 80%. An octanoyl acyl group was used as anchor for the PEG moiety (PEG-CerC8) permitting a quick exchange out of the SPLP to further optimize the in vitro and in vivo transfection. We have demonstrated that this technique can be used to encapsulate either linearized DNA or supercoiled plasmids ranging from 3-20 kb. The SPLP formed could be isolated from empty vesicles by sucrose density gradient centrifugation, and exhibited a narrow size distribution of approximately 75 +/- 6 nm as determined by cryo-electron microscopy. The high plasmid-to-lipid ratio observed corresponded to one plasmid per particle. The SPLP consist of a lipid bilayer surrounding the plasmid DNA as visualized by cryo-electron microscopy. SPLP containing a range of DODAC concentrations were tested for in vitro and in vivo transfection. In vitro, in COS-7 cells transfection reached a maximum after 48 h. The transfection efficiency increased when the DODAC concentration in the SPLP was decreased from 42.5 to 24 mol% DODAC. Decreasing the cationic lipid concentration improved transfection in part due to decreased toxicity. In vivo studies using an intraperitoneal B16 tumor model and intraperitoneal administration of SPLP showed maximum transfection activity for SPLP containing 24 mol% DODAC. Gene expression observed in tumor cells was increased by approximately one magnitude as compared to cationic lipid/DNA complexes. The SPLP were stable and upon storage at 4 degrees C no significant change in the transfection activity was observed over a one-year period. Thus this phosphate buffer detergent dialysis technique can be used to generate SPLP formulations containing a wide range of cationic lipid concentrations to determine optimal SPLP composition for high transfection activity and low toxicity.     

Reducing risks associated with drinking among young adults: promoting knowledge-based perspectives and harm reduction strategies

The situation with regard to drinking is particularly complex for young adults: they are typically faced with pressures on one hand to abstain or drink small quantities, and on the other hand there may be expectations to drink heroic amounts and engage in risk-taking while drinking. Furthermore, in some cultures a very short transition period time is evident between condoned occasional experimentation with alcohol and the expectations of being able to manage alcohol use in a wide range of settings. Also, the perceived invincibility among youth stands in sharp contrast to their high rates of traumatic events involving alcohol. The paper by Barbara Leigh examines the nature and dimensions of risk-taking particularly among young adults. For example, her analysis encourages us to look beyond preliminary associations about the proportion of certain events where drinking was involved, and consider whether drinking was a correlate or a contributing cause. The paper by James Mosher points to the importance of obtaining information about the population, situation and drinker as a basis for population-level interventions, involving environmental changes in the promotion and distribution of alcoholic beverages. The papers point to a search for interventions that are distinguished by their effectiveness in reducing harm, and not necessarily by their faddish value. An essential step is drawing the younger drinker into an accurate documentation of risk-taking experiences, and also in collaborating in developing humane, reasonable and effective approaches in reducing drinking-related harm.     

A case-crossover study of acute alcohol use and suicide attempt

OBJECTIVE: Several studies have shown that acute alcohol use is associated with suicidal behavior, but the magnitude and nature of the relationship remain unclear. We report a study on the impact of acute alcohol use on suicide attempts treated in the emergency room (ER) using the case-crossover design. METHOD: Seven ER studies carried out in the United States, Canada, Mexico and Australia from 1984 to 1996 with probability samples and similar methodology were merged yielding a total of 102 suicide attempters (overall 52% were male and 59% under 30 years of age). RESULTS: Thirty-six patients reported alcohol use within 6 hours prior to the suicide attempt. When usual alcohol consumption during the past 12 months served as the control value, the estimated relative risk (RR) for patients who reported alcohol use within 6 hours prior to the suicide attempt was 9.6 (95% confidence interval: 5.7-16.3). Although the prevalence of alcohol use differed by sex, there was no statistically significant difference in the estimated RRs (RR = 13.6 men and RR = 5.3 women, p = 0.11 for the heterogeneity test). CONCLUSIONS: A positive association was found between alcohol use 6 hours prior and suicide attempts in 102 ER cases in four countries. The case-crossover methodology is well suited to studies for which an external control group is not easily obtainable.