Muscle exercise in limb girdle muscular dystrophies: pitfall and advantages

Different genetic mutations underlying distinct pathogenic mechanisms have been identified as cause of muscle fibers degeneration and strength loss in limb girdle muscular dystrophies (LGMD). As a consequence, exercise tolerance is affected in patients with LGMD, either as a direct consequence of the loss of muscle fibers or secondary to the sedentary lifestyle due to the motor impairment. It has been debated for many years whether or not muscle exercise is beneficial or harmful for patients with myopathic disorders. In fact, muscular exercise would be considered in helping to hinder the loss of muscle tissue and strength. On the other hand, muscle structural defects in LGMD can result in instability of the sarcolemma, making it more likely to induce muscle damage as a consequence of intense muscle contraction, such as that performed during eccentric training. Several reports have suggested that supervised aerobic exercise training is safe and may be considered effective in improving oxidative capacity and muscle function in patients with LGMD, such as LGMD2I, LGMD2L, LGMD2A. More or less comfortable investigation methods applied to assess muscle function and structure can be useful to detect the beneficial effects of supervised training in LGMD. However, it is important to note that the available trials assessing muscle exercise in patients with LGMD have often involved a small number of patients, with a wide clinical heterogeneity and a different experimental design. Based on these considerations, resistance training can be considered part of the rehabilitation program for patients with a limb-girdle type of muscular dystrophy, but it should be strictly supervised to assess its effects and prevent possible development of muscle damage.Key words: limb girdle muscle dystrophies, muscle fatigue, muscle exercise     

FREE THYROXINE (FT4) AND FREE TRIIODOTHYRONINE (FT3) IN AUTONOMOUS THYROID NODULES

Total and free thyroid hormones (T3, T4, FT3 and FT4), TSH and its response to TRH were determined in sixty-three patients affected by autonomous thyroid nodules: mean concentrations of free T3 (FT3) were significantly higher in hot nodules (suppressing extranodular tissue on the scan) as compared to warm ones, even in those cases where total T3 and T4 were within normal ranges (hot nodules, group as a whole: 8.8 +/- 3.5 pg/ml; warm nodules: 5.3 +/- 1.2; hot nodules with normal total T3 and T4 concentrations: 7.5 +/- 3). Also the clinical condition of thyrotoxicosis appeared to be correlated with FT3 concentrations (toxic patients, group as a whole: 9.6 +/- 4.0 pg/ml; euthyroid patients: 6.8 +/- 3.1; toxic patients with normal values of T3 and T4; 8.3 +/- 2.8). On the contrary the correlation of total and free thyroid hormone concentrations with the response of TSH to TRH was not significant.     

A Meta‐Analysis of Sex‐Related Differences in Outcomes After Primary Percutaneous Intervention for ST‐Segment Elevation Myocardial Infarction

Introduction

The increasing use of primary percutaneous coronary intervention (pPCI) has improved clinical outcome in ST‐segment elevation myocardial infarction (STEMI) patients, but the impact of sex on early and mid‐term outcomes remains to be defined.

Methods

Medline, Cochrane Library, Biomed Central, and Google Scholar were searched for articles describing differences in baseline, periprocedural, and midterm outcomes after pPCI, by sex. The primary end point was all‐cause mortality at early and mid‐term follow‐up. Secondary endpoints included in‐hospital bleeding and stroke.

Results

Sixteen studies were included. Women were older, had more frequent hypertension, diabetes mellitus, and hypercholesterolemia, as well as longer ischemia time and more shock at presentation. Men were more likely to have had a previous myocardial infarction. Female sex emerged as independently associated to early mortality (OR 1.1; 95%CI, 1.02–1.18) but not to mid‐term mortality (OR, 1.01; 95%CI, 0.99–1.03). The pooled analysis showed a significantly higher risk of in hospital stroke (OR, 1.69; 95%CI, 1.11–2.56) and major bleeding (OR, 2.04; 95%CI, 1.51–2.77) in women.

Conclusions

As compared to men, women undergoing pPCI have more bleedings and strokes, and a worse early, but not mid‐term mortality. These findings may allow a better risk stratification of pPCI patients.

     

EFFECT OF EARLY BLOCKADE OF BRADYKININ B2-RECEPTORS ON THE BLOOD PRESSURE PHENOTYPE OF NORMOTENSIVE AND SPONTANEOUSLY HYPERTENSIVE RATS

We evaluated if chronic blockade of bradykinin B₂-receptors by the long-acting antagonist Icatibant (D-Arg,‘Hyp³,Thi⁵,D-Tic⁷,Oic⁸’-bradykinin) affects blood pressure of rats. Pairs of normotensive Wistar Kyoto rats or spontaneously hypertensive rats were mated and their offspring received Icatibant (25 nmol day⁻¹per kg body wt., s.c.) or vehicle from the 2nd day until the 7th week of life. Then, the administration of Icatibant or vehicle was continued by i.p. infusion using Alzet osmotic pumps. At 9 weeks of age, normotensive rats given Icatibant showed greater systolic blood pressure (135±1vs115±1 mmHg in vehicle-treated rats,P<0.01), while heart rate was similar. The group difference regarding blood pressure levels was confirmed by direct intra-arterial measurement. No difference was detected between vehicle- and Icatibant-treated spontaneously hypertensive rats regarding blood pressure increase with aging. In conclusion, chronic blockade of bradykinin receptors by Icatibant alters the adult cardiovascular phenotype of Wistar Kyoto rats, provided that the antagonist is given at the early phases of life. These results suggest that the B₂-receptor is essential for the maintenance of cardiovascular homeostasis during development, whereas it does not exert a protective role against the progression of hypertension in a rat model of genetic hypertension.     

Chronic treatment with I-dopa plus carbidopa in hemitransected rats: Preferential effects at intact dopamine synapses leading to behavioural signs of dopamine receptor supersensitivity

Chronic i. p. treatment with 1-dopa-carbidopa for 3 weeks in hemitransected male rats leads on one hand to tolerance to l-dopa induced turning behaviour and on the other hand to behavioural and biochemical signs of dopamine (DA) receptor supersensitivity on the intact side. Thus, the apomorphine induced ipsilateral turning behaviour is enhanced and the K_d values of the ³H-spiperone binding sites linked to DA receptors of the D₂ type on the intact, but not on the denervated side are reduced by 40%. However, the number of ³H-spiperone binding sites is reduced by 20% in striatal membranes on the intact side after this type of treatment. Therefore, chronic treatment with a catecholamine (CA) precursor leads to selective adaptive changes at intact striatal DA synapses with certain signs of the expected development of DA receptor subsensitivity, but above all with signs of paradoxical development of DA receptor supersensitivity. A hypothesis is introduced to explain these results.