Ranolazine-induced lipid storage myopathy presenting with respiratory failure and head drop.

Ranolazine is an anti-ischemic drug often used along with statins in patients with ischemic heart disease. Ranolazine-induced proximal myopathy or rhabdomyolysis have been rarely reported, but toxic effects of statins could not be completely ruled out in those cases. We report a 68-year-old man with ranolazine-induced myopathy who presented with respiratory insufficiency and head drop. Creatine kinase level was normal. The Patient continued to worsen despite statin cessation but markedly improved after stopping ranolazine. Muscle biopsy showed excessive lipid accumulation predominantly in type 1 myofibers. The precise mechanism of toxicity is not clear. Treating physicians should be aware of this rare but potentially debilitating adverse effect of ranolazine. Prognosis is good upon discontinuation of the offending drug.

Sugammadex antagoniza el bloqueo neuromuscular provocado por rocuronio en dos tipos de trastornos neuromusculares: distrofia miotónica y atrofia muscular espinal / Sugammadex reversal of rocuronium-induced neuromuscular blockade in two types of neuromuscular disorders: Myotonic dystrophy and spinal muscular atrophy

Las enfermedades neuromusculares como la distrofia miotónica (o enfermedad de Steinert) y la atrofia muscular espinal se asocian con las complicaciones perioperatorias relacionadas con la debilidad muscular. Estos pacientes presentan una hipersensibilidad a los bloqueantes neuromusculares no despolarizantes que podría derivar en curarización residual postoperatoria con complicaciones respiratorias. Para evitarlo conviene antagonizar satisfactoriamente el bloqueo neuromuscular (BNM). Sugammadex es el primer relajante selectivo y antagoniza los bloqueos neuromusculares por rocuronio y vecuronio. Se notifican dos casos donde los pacientes recibieron sugammadex para antagonizar un bloqueo neuromuscular provocado por rocuronio. El antagonismo de los BNM por rocuronio en ambos casos fue rápido, eficaz y sin recurarización, no se observaron preocupaciones de seguridad(AU)

Neuromuscular disorders like myotonic dystrophy (dystrophia myotonica or Steinert's disease) and spinal muscular atrophy are associated with perioperative complications related to muscle weakness. These patients have an increased sensitivity to non-depolarising neuromuscular blocking agents, which can lead to postoperative residual curarization (PORC) and its associated respiratory complications. Adequate reversal of neuromuscular blockade is essential to prevent this. Sugammadex is the first selective relaxant binding agent and it reverses rocuronium- and vecuronium-induced neuromuscular block. Two cases are reported in which the patients received sugammadex to reverse a rocuronium-induced neuromuscular block. Reversal of the rocuronium-induced neuromuscular block (NMB) in both cases was fast, effective and without recurarization, and no safety concerns were observed(AU)

Manganese exposure induces microglia activation and dystrophy in the substantia nigra of non-human primates.

Chronic manganese (Mn) exposure produces neurological deficits including a form of parkinsonism that is different from Parkinson's disease (PD). In chronic Mn exposure, dopamine neurons in the substantia nigra (SN) do not degenerate but they appear to be dysfunctional. Further, previous studies have suggested that the substantia nigra pars reticulata (SNr) is affected by Mn. In the present study, we investigated whether chronic Mn exposure induces microglia activation in the substantia nigra pars compacta (SNc) and SNr in Cynomolgus macaques. Animals were exposed to different weekly doses of Mn (3.3-5.0, 5.0-6.7, 8.3-10 mg Mn/kg body weight) and microglia were examined in the substantia nigra using LN3 immunohistochemistry. We observed that in control animals, LN3 labeled microglia were characterized by a resting phenotype. However, in Mn-treated animals, microglia increased in number and displayed reactive changes with increasing Mn exposure. This effect was more prominent in the SNr than in the SNc. In the SNr of animals administered the highest Mn dose, microglia activation was the most advanced and included dystrophic changes. Reactive microglia expressed increased iNOS, L-ferritin, and intracellular ferric iron which were particularly prominent in dystrophic compartments. Our observations indicate that moderate Mn exposure produces structural changes on microglia, which may have significant consequences on their function.

Mouse model of skeletal muscle adiposity: a glycerol treatment approach.

Fat cell accumulation in skeletal muscle is a major characteristic of various disorders, such as obesity, sarcopenia and dystrophies. Moreover, these fat cells could be involved in muscle homeostasis regulation as previously described for adipocytes in bone marrow. Despite recent advances on the topic, no clearly characterized mouse model is currently available to study fat accumulation within skeletal muscle. Here, we report a detailed characterization of a mouse model of skeletal muscle fat cell accumulation after degeneration induced by intra-muscular injection of glycerol. Information is provided on the kinetics of degeneration/fat deposition, including the quantity of fat deposited based on various parameters such as glycerol concentration, age, sex and strain of mice. Finally, these fat cells are characterized as true white adipocytes morphologically and molecularly. Our study shows that the mouse adipocyte accumulation within skeletal muscle after glycerol degeneration is a reproducible, transposable and easy model to use. This mouse model should allow a more comprehensive understanding of the impact of adipocyte accumulation in skeletal muscle pathophysiology.

Subjective muscle weakness and hypotonia during clozapine treatment.

Four cases of patients who described an unpleasant subjective experience of weakness and reduced muscle tone during treatment with clozapine are presented. An exacerbation of muscular dystrophy during clozapine treatment is also described. It is hypothesized that these adverse effects are related to the muscle relaxant properties of clozapine. The differential diagnosis of sedation, fatigue, asthenia, and reduced muscle tone is discussed.

Efeitos do cloridrato de tetraciclina em fetos de ratas tratadas com o antibiótico (Rattus Norvegicus, raça Wistar, var. Albinus, Rodentia) / Effects of tetracyclin hydrochloride in fetus of rats treated with antibiotic (Rattus Norvegicus, raça Wistar, var. Albinus, Rodentia)

Os autores utilizaram ratas prenhas, em diversos períodos de prenhez, nas quais foi administrada, em dose única, o cloridrato de tetraciclina por via intraperitoneal. No 21§ dia da prenhez, as ratas foram submetidas a cesarianas, quando entäo foi contado o número de implantes ou reabsorçöes, e o número de fetos de cada corno uterino. Processou-se posteriormente à análise histológica de alguns fetos obtidos em diversos períodos da prenhez, para evidenciar-se a distrofia adiposa hepática; relacionando-se entäo a toxicidade da droga para fetos de ratas, em virtude da dose e do tempo de prenhez das ratas utilizadas

[Metabolic status in workers engaged in the production of cobalt-containing powder compositions of hard alloys]. / Sostoianie metabolizma u rabochikh proizvodstva kobal'tsoderzhashchikh poroshkovykh kompozitsii tverdykh splavov.

A wide-range complex of biochemical techniques was used to study metabolic processes in workers exposed to cobalt and ethanol. In practically healthy workers were found laboratory manifestations of hepato-biliary irritations, hyperpermeability of the hepatocytes' cytoplasmic membrane, cholestasis syndrome, initial manifestations of muscular dystrophy and minor signs of atherosclerosis risks. The biochemical shifts were like those in alcoholism cases. It was suggested that, under the existing technological conditions of cobalt-containing hard-facing alloys' powder processing, the action of ethanol increased the toxic effect of cobalt.

Inhibition of prostaglandin synthesis produces a muscular dystrophy-like myopathy.

Administration of inhibitors of prostaglandin synthetase to chicken embryos produced myopathies in their skeletal muscles which were characterized by ringbinden, hypercontraction, loss of Z disks, M bands, and thick and thin filaments. The effects of the inhibitors were reversed by administration of PGE1. The pathology of the myopathy induced in the chicken embryos was identical to that observed in human muscular dystrophy and had some features in common with other congenital myopathies. Altered prostaglandin function may therefore be directly or indirectly involved in the pathogenesis of congenital myopathies.

Myotonic muscular dystrophy associated with ritodrine tocolysis.

A patient thought to be normal was admitted with premature labor at 29+ weeks' gestation. Treatment with the beta-mimetic ritodrine hydrochloride appeared to provoke symptoms of myotonic muscular dystrophy. Neurological history and examination confirmed the presence of previously unsuspected myotonic dystrophy in the patient, her father, and paternal grandfather. Discontinuation of the drug led to improvement in myotonia symptoms but worsening premature labor. Magnesium sulfate did not provoke the same symptoms but was unsuccessful in controlling premature contractions. Long-term management with bed rest, phenytoin, and isoxsuprine hydrochloride resulted in term delivery. Subsequently, maternal symptoms of myotonia disappeared. Congenital myotonia was suspected in the fetus because of the ultrasonic demonstration of polyhydramnios and reduced fetal movements. This was confirmed at delivery. The mechanism by which ritodrine unmasked the myotonia is unclear but may be related to changes in the cell membrane (chloride conductance, the sodium-potassium pump, or membrane polarization).

Muscular dystrophy in mice after chronic subcutaneous treatment with cannabinoids.

Swiss male albino mice were treated subcutaneously with the main cannabinoids (CBN, CBD, delta9-THC) at the dosage of 1 mg/kg per day for 30 days, and with the crude resin. At the end of the treatment, after supramaximal stimulation of the sciatic nerve, a significant decrease of both maximal twitch and tetanus tensions was observed in delta9-THC-treated animals; CBD and resin treatment produced some decrease in active tension, while CBN treatment induced an enhancement of the contractile strength. Histology showed lesions interpretable as due to muscular dystrophy. Analysis of protein and hydroxyproline muscular content showed a marked reduction in protein in all treated animals, with a corresponding high increase in hydroxyproline content.

Skeletal muscle necrosis following membrane-active drugs plus serotonin.

Administration of imipramine plus serotonin (5-HT) to rats has been proposed as an animal model of Duchenne muscular dystrophy. We studied the skeletal muscle necrosis produced in male rats given 5-HT after pretreatment with imipramine, other tricyclic antidepressants, or antihistamines, which like the tricyclic antidepressants, can block neuronal reuptake of 5-HT. Following one of these agents plus 5-HT, 20 mg/kg subcutaneously (s.c.), necrosis was more severe in the soleus muscle than the quadriceps. There was no significant difference in the incidence of necrosis in the soleus and quadriceps muscles following one of these agents plus 5-HT, 100 mg/kg, intraperitoneally (i.p.). After one of these agents plus 5-HT i.p., but not 5-HT s.c., extensive necrosis was significantly more frequent and severe in the quadriceps muscle than after 5-HT s.c. Chlorpheniramine (CP) plus 5-HT, 2.5 mg/kg intravenously, produced less muscle necrosis than CP plus 5-HT s.c. or i.p. The necrosis produced by CP plus 5-HT s.c. was comparable ipsilateral and contralateral to the injection site. The necrosis following CP plus 5-HT i.p. was maximal at 24 hr and remained fairly constant until 5 days. Regeneration was prominent by 7 days. The muscle necrosis produced by CP plus 5-HT is blocked by some 5-HT blockers, e.g., methiotepin and methysergide. It is also partially blocked by denervation. The capacity of tricyclic antidepressants and antihistamines to block neuronal 5-HT reuptake tended to be negatively correlated with the capacity to potentiate the muscle necrosis they produced with 5-HT, which suggests that blockade of 5-HT uptake is not the mechanism of the pathology produced by the combined treatment. The tricyclic antidepressants and the antihistamines are "membrane stabilizers-labilizers". Other drugs which are "membrane stabilizers-labilizers" such as trihexyphenidyl and procaine also promoted skeletal muscle necrosis when given prior to 5-HT. It is proposed that the effects of imipramine plus 5-HT on skeletal muscle are not due to the blockade of neuronal uptake of 5-HT and subsequent vascular-induced ischemia, but reflect direct toxic effects of these agents on skeletal muscle.