Mitochondrial function following downhill and/or uphill exercise training in rats

Introduction: The goal of this study was to compare the effects of downhill (DH), uphill (UH), and UH‐DH exercise training, at the same metabolic rate, on exercise capacity and skeletal muscle mitochondrial function. Methods: Thirty‐two Wistar rats were separated into a control and 3 trained groups. The trained groups exercised for 4 weeks, 5 times per week at the same metabolic rate, either in UH, DH, or combined UH‐DH. Twenty‐four hours after the last training session, the soleus, gastrocnemius, and vastus intermedius muscles were removed for assessment of mitochondrial respiration. Results: Exercise training, at the same metabolic rate, improved maximal running speed without specificity for exercise modalities. Maximal fiber respiration was enhanced in soleus and vastus intermedius in the UH group only. Conclusions: Exercise training, performed at the same metabolic rate, improved exercise capacity, but only UH‐trained rats enhanced mitochondrial function in both soleus and vastus intermedius skeletal muscle. Muscle Nerve 54 : 925–935, 2016     

“Red‐flag” symptom clusters in transthyretin familial amyloid polyneuropathy

Transthyretin familial amyloid polyneuropathy (TTR‐FAP) is a rare, progressive, life‐threatening, hereditary disorder caused by mutations in the transthyretin gene and characterized by extracellular deposition of transthyretin‐derived amyloid fibrils in peripheral and autonomic nerves, heart, and other organs. TTR‐FAP is frequently diagnosed late because the disease is difficult to recognize due to phenotypic heterogeneity. Based on published literature and expert opinion, symptom clusters suggesting TTR‐FAP are reviewed, and practical guidance to facilitate earlier diagnosis is provided. TTR‐FAP should be suspected if progressive peripheral sensory‐motor neuropathy is observed in combination with one or more of the following: family history of a neuropathy, autonomic dysfunction, cardiac hypertrophy, gastrointestinal problems, inexplicable weight loss, carpal tunnel syndrome, renal impairment, or ocular involvement. If TTR‐FAP is suspected, transthyretin genotyping, confirmation of amyloid in tissue biopsy, large‐ and small‐fiber assessment by nerve conduction studies and autonomic system evaluations, and cardiac testing should be performed.     

Tau phosphorylation‐associated spine regression does not impair hippocampal‐dependent memory in hibernating golden hamsters

The microtubule‐associated protein tau, in its hyperphosphorylated form, is the major component of paired helical filaments and other aggregates in neurodegenerative disorders commonly referred to as “tauopathies”. Recent evidence, however, indicates that mislocalization of hyperphosphorylated tau to subsynaptic sites leads to synaptic impairment and cognitive decline even long before formation of tau aggregates and neurodegeneration occur. A similar, but reversible hyperphosphorylation of tau occurs under physiologically controlled conditions during hibernation. Here, we study the hibernating Golden hamster (Syrian hamster, Mesocricetus auratus). A transient spine reduction was observed in the hippocampus, especially on apical dendrites of hippocampal CA3 pyramidal cells, but not on their basal dendrites. This distribution of structural synaptic regression was correlated to the distribution of phosphorylated tau, which was highly abundant in apical dendrites but hardly detectable in basal dendrites. Surprisingly, hippocampal memory assessed by a labyrinth maze was not affected by hibernation. The present study suggests a role for soluble hyperphosphorylated tau in the process of reversible synaptic regression, which does not lead to memory impairment during hibernation. We hypothesize that tau phosphorylation associated spine regression might mainly affect unstable/dynamic spines while sparing established/stable spines. © 2015 Wiley Periodicals, Inc.     

In vitro interactions of approved and novel drugs against Paecilomyces spp

We have evaluated the in vitro activity of 15 combinations of antifungal drugs (amphotericin B, itraconazole, voriconazole, albaconazole, ravuconazole, terbinafine, and micafungin) against four isolates of Paecilomyces variotii and three of P. lilacinus. The interaction of terbinafine with the four azoles was synergistic for 53% of the combinations, while the interactions of both amphotericin B and micafungin with the rest of antifungal agents were mainly indifferent.     

Prevalence of and referred pain from myofascial trigger points in the forearm muscles in patients with lateral epicondylalgia

OBJECTIVE: Referred pain and pain characteristics evoked from the extensor carpi radialis brevis, extensor carpi radialis longus, extensor digitorum communis, and brachioradialis muscles was investigated in 20 patients with lateral epicondylalgia (LE) and 20-matched controls. METHODS: Both groups were examined for the presence of myofascial trigger points (TrPs) in a blinded fashion. The quality and location of the evoked referred pain, and the pressure pain threshold (PPT) at the lateral epicondyle on the right upper extremity (symptomatic side in patients, and dominant-side on controls) were recorded. Several lateral elbow pain parameters were also evaluated. RESULTS: Within the patient group, the elicited referred pain by manual exploration of 13 out of 20 (65%) extensor carpi radialis brevis muscles, 12/20 (70%) extensor carpi radialis longus muscles, 10/20 (50%) brachioradialis muscles, and 5/20 (25%) extensor digitorum communis muscles, shares similar pain patterns as their habitual lateral elbow and forearm pain. The mean number of muscles with TrPs for each patient was 2.9 [95% confidence interval (CI) 1,4] of which 2 (95% CI 1,3) were active, and 0.9 (95% CI 0,2) were latent TrPs. Control participants only had latent TrPs (mean: 0.4; 95% CI 0,2). TrP occurrence between the 2 groups was significantly different for active TrPs (P<0.001), but not for latent TrPs (P>0.05). The referred pain pattern was larger in patients than in controls, with pain referral to the lateral epicondyle (proximally) and to the dorso-lateral aspect of the forearm in the patients, and confined to the dorso-lateral aspect of the forearm in the controls. Patients with LE showed a significant (P<0.001) lower PPT (mean: 2.1 kg/cm; 95% CI 0.8, 4 kg/cm) as compared with controls (mean: 4.5 kg/cm; 95% CI 3, 7 kg/cm). Within the patient group, PPT at the lateral epicondyle was negatively correlated with both the total number of TrPs (rs=-0.63; P=0.003) and the number of active TrPs (rs=-0.5; P=0.02): the greater the number of active TrPs, the lower the PPT at the lateral epicondyle. DISCUSSION: Our results suggest that in patients with LE, the evoked referred pain and its sensory characteristics shared similar patterns as their habitual elbow and forearm pain, consistent with active TrPs. Lower PPT and larger referred pain patterns suggest that peripheral and central sensitization exists in LE.