Relevance of pathogenicity prediction tools in human RYR1 variants of unknown significance.

Malignant hyperthermia (MH) is a pharmacogenetic disorder of skeletal muscle metabolism characterized by generalized muscle rigidity, increased body temperature, rhabdomyolysis, hyperkalemia and severe metabolic acidosis. The underlying mechanism of MH involves excessive Ca release from myotubes via the ryanodine receptor type 1 (RYR1) and the voltage-dependent L-type calcium channel (CACNA1S). As more than 300 variants of unknown significance have been detected to date, we examined whether freely available pathogenicity prediction tools are able to detect relevant MH causing variants.

Paxilline Prevents the Onset of Myotonic Stiffness in Pharmacologically Induced Myotonia: A Preclinical Investigation.

Reduced Cl conductance causes inhibited muscle relaxation after forceful voluntary contraction due to muscle membrane hyperexcitability. This represents the pathomechanism of myotonia congenita. Due to the prevailing data suggesting that an increased potassium level is a main contributor, we studied the effect of a modulator of a big conductance Ca- and voltage-activated K channels (BK) modulator on contraction and relaxation of slow- and high-twitch muscle specimen before and after the pharmacological induction of myotonia.

The Stiffness Comparison Test: A pilot study to determine inter-individual differences in palpatory skill related to gender, age, and occupation-related experience.

Background: Manual palpation is a core skill in physical examination. Assessing elastic properties such as tissue stiffness has the potential for being an important diagnostics tool in the detection of cancer and other diseases.

Objective: The study describes the newly developed Stiffness Comparison Test (SCT).

Correction to: Preclinical pharmacological in vitro investigations on low chloride conductance myotonia: effects of potassium regulation.

The original article contains an error during online publication. Table 2 was included during production round and now deleted. The Original article has been corrected.

Preclinical pharmacological in vitro investigations on low chloride conductance myotonia: effects of potassium regulation.

In myotonia, reduced Cl conductance of the mutated ClC-1 channels causes hindered muscle relaxation after forceful voluntary contraction due to muscle membrane hyperexcitability. Repetitive contraction temporarily decreases myotonia, a phenomena called "warm up." The underlying mechanism for the reduction of hyperexcitability in warm-up is currently unknown.

Structural and Functional Changes in the Coupling of Fascial Tissue, Skeletal Muscle, and Nerves During Aging.

Aging is a one-way process associated with profound structural and functional changes in the organism. Indeed, the neuromuscular system undergoes a wide remodeling, which involves muscles, fascia, and the central and peripheral nervous systems. As a result, intrinsic features of tissues, as well as their functional and structural coupling, are affected and a decline in overall physical performance occurs.

Elevation of extracellular osmolarity improves signs of myotonia congenita in vitro: a preclinical animal study.

Key Points: During myotonia congenita, reduced chloride (Cl ) conductance results in impaired muscle relaxation and increased muscle stiffness after forceful voluntary contraction. Repetitive contraction of myotonic muscle decreases or even abolishes myotonic muscle stiffness, a phenomenon called 'warm up'. Pharmacological inhibition of low Cl channels by anthracene-9-carboxylic acid in muscle from mice and ADR ('arrested development of righting response') muscle from mice showed a relaxation deficit under physiological conditions compared to wild-type muscle.

Hypermetabolism in B-lymphocytes from malignant hyperthermia susceptible individuals.

Malignant hyperthermia (MH) is a pharmacogenetic disorder of skeletal muscle metabolism which is characterized by generalized muscle rigidity, increased body temperature, rhabdomyolysis, and severe metabolic acidosis. The underlying mechanism of MH involves excessive Ca(2+) release in myotubes via the ryanodine receptor type 1 (RyR1). As RyR1 is also expressed in B-lymphocytes, this study investigated whether cellular metabolism of native B-lymphocytes was also altered in MH susceptible (MHS) individuals.

Effects of intravenous sulfide during resuscitated porcine hemorrhagic shock*.

Objective: Controversial data are available on the effects of hydrogen sulfide during hemorrhage. Because the clinical significance of hydrogen sulfide administration in rodents may not be applicable to larger species, we tested the hypothesis whether intravenous Na2S (sulfide) would beneficially influence organ dysfunction during long-term, porcine hemorrhage and resuscitation.

Design: Prospective, controlled, randomized study.