Early or advanced stage type 2 diabetes is not accompanied by in vivo skeletal muscle mitochondrial dysfunction

Objective: Several lines of evidence support a potential role of skeletal muscle mitochondrial dysfunction in the pathogenesis of insulin resistance and/or type 2 diabetes. However, it remains to be established whether mitochondrial dysfunction represents either cause or consequence of the disease. We examined in vivo skeletal muscle mitochondrial function in early and advanced stages of type 2 diabetes, with the aim to gain insight in the proposed role of mitochondrial dysfunction in the aetiology of insulin resistance and/or type 2 diabetes. Methods: Ten long-standing, insulin-treated type 2 diabetes patients, 11 subjects with impaired fasting glucose, impaired glucose tolerance and/ or recently diagnosed type 2 diabetes, and 12 healthy, normoglycaemic controls, matched for age and body composition and with low habitual physical activity levels were studied. In vivo mitochondrial function of the vastus lateralis muscle was evaluated from post-exercise phosphocreatine (PCr) recovery kinetics using 31P magnetic resonance spectroscopy (MRS). Intramyocellular lipid (IMCL) content was assessed in the same muscle using single-voxel 1H MRS. Results: IMCL content tended to be higher in the type 2 diabetes patients when compared with normoglycaemic controls (P=0.06). The 31P MRS parameters for mitochondrial function, i.e. PCr and ADP recovery time constants and maximum aerobic capacity, did not differ between groups. Conclusions: The finding that in vivo skeletal muscle oxidative capacity does not differ between long-standing, insulin-treated type 2 diabetes patients, subjects with early stage type 2 diabetes and sedentary, normoglycaemic controls suggests that mitochondrial dysfunction does not necessarily represent either cause or consequence of insulin resistance and/or type 2 diabetes. © 2008 Society of the European Journal of Endocrinology

No evidence for distinguishing bacterial from viral acute rhinosinusitis using symptom duration and purulent rhinorrhea: a systematic review of the evidence base

OBJECTIVE: To evaluate the diagnostic value of symptom duration and purulent rhinorrhea in adults suspected of having acute bacterial rhinosinusitis. DATA SOURCES: PubMed, EMBASE, and the Cochrane Library. REVIEW METHODS: We performed a comprehensive systematic search on March 28, 2013. We included studies on the diagnostic value of duration of symptoms and purulent rhinorrhea in patients suspected of having acute bacterial rhinosinusitis. We assessed study design of included articles for directness of evidence and risk of bias. We extracted prevalence and positive and negative predictive values. RESULTS: Of 4173 unique publications, we included 1 study with high directness of evidence and moderate risk of bias. The prior probability of bacterial rhinosinusitis was 0.29 (95% confidence interval [CI], 0.24-0.35); we could not extract posterior probabilities. Odds ratios (95% CI) from univariate analysis were 1.03 (0.78-1.36) for duration of symptoms and 2.69 (1.39-5.18) for colored discharge on the floor of the nasal cavity. CONCLUSION AND RECOMMENDATION: We included 1 study with moderate risk of bias, reporting data in such a manner that we could not assess the value of symptom duration and purulent rhinorrhea in adults suspected of having acute bacterial rhinosinusitis. Recommendations to distinguish between a viral and a bacterial source based on purulent rhinorrhea are not supported by evidence, and the decision to prescribe antibiotic treatment should not depend on its presence. Based on judgment driven by theory and subsidiary evidence of a greater likelihood of bacterial rhinosinusitis after 10 days, antibiotic therapy may seem a reasonable empirical option

Do cannabinoid antagonists affect cognition? SLV326 induces changes in theta and gamma bands in active rats

19th biennial IPEG Meeting: Nijmegen, The Netherlands. 26-30 October 2016. Cannabinoid CB1 antagonists have been investigated for possible treatment of e.g. obesity-related disorders. However, clinical application was halted due to their symptoms of anxiety and depression. In addition to these adverse effects, we have shown earlier that chronic treatment with the CB1 antagonist rimonabant may induce convulsive seizures which were EEG-confirmed. However, due to the wide distribution of CB1 receptors throughout the CNS, it is highly unlikely that chronic blocking of the CB1 receptor is only manifested in seizures. CB1 agonists have been described to alter the EEG frequency spectrum. No such data are available for CB antagonists. In a regulatory repeat-dose toxicity study "muscle spasms" were observed in Wistar rats, daily dosed with the CB1 receptor antagonist SLV326 during 5 months. In selected SLV326-treated and control animals, EEG and behavior were monitored for 24 h. Subsequently, random segments of the interictal EEG were selected, totaling 20 min per animal. These segments were assigned to subsets of 'active state' or 'passive state', based on Passive Infrared (PIR) motion detection. Spectral information was calculated using a Fast Fourier Transformation analysis. 25 % of SLV326 treated animals showed, EEG-confirmed, spontaneously occurring generalized convulsive seizures, whereas all controls were seizure-free. The behavioral signs of the seizures were typical for a limbic origin. The frequency spectrum of the interictal EEG of the treated rats showed a lower theta peak frequency, as well as lower gamma power compared to the controls. These frequency changes were state-dependent: they were only found during high locomotor activity. However, the treatment did not affect the amount of locomotor activity itself. Apart from confirming our previous finding that long-term blockade of the endogenous cannabinoid system can provoke limbic seizures in otherwise healthy rats, this study shows that SLV326 alters the frequency spectrum of the EEG, but only when rats are highly active. It is therefore likely that the EEG effects caused by SLV326 are linked to higher order behavior that might be present during locomotion. Theta rhythm is shown to be a marker of complex behavior, and gamma rhythm is typically associated with cognitive functions. Therefore, these observations suggest that CB antagonists might have effects on complex behavior and cognition