Structural and functional alterations of the cell nucleus in skeletal muscle wasting: the evidence in situ

The histochemical and ultrastructural analysis of the nuclear components involved in RNA transcription and splicing can reveal the occurrence of cellular dysfunctions eventually related to the onset of a pathological phenotype. In recent years, nuclear histochemistry at light and electron microscopy has increasingly been used to investigate the basic mechanisms of skeletal muscle diseases; the in situ study of nuclei of myofibres and satellite cells proved to be crucial for understanding the pathogenesis of skeletal muscle wasting in sarcopenia, myotonic dystrophy and laminopathies

Clinical aspects, molecular pathomechanisms and management of myotonic dystrophies

Myotonic dystrophy (DM) is the most common adult muscular dystrophy, characterized by autosomal dominant progressive myopathy, myotonia and multiorgan involvement. To date two distinct forms caused by similar mutations have been identified. Myotonic dystrophy type 1 (DM1, Steinert's disease) was described more than 100 years ago and is caused by a (CTG)n expansion in DMPK, while myotonic dystrophy type 2 (DM2) was identified only 18 years ago and is caused by a (CCTG)n expansion in ZNF9/CNBP. When transcribed into CUG/CCUG-containing RNA, mutant transcripts aggregate as nuclear foci that sequester RNA-binding proteins, resulting in spliceopathy of downstream effector genes. Despite clinical and genetic similarities, DM1 and DM2 are distinct disorders requiring different diagnostic and management strategies. DM1 may present in four different forms: congenital, early childhood, adult onset and late-onset oligosymptomatic DM1. Congenital DM1 is the most severe form of DM characterized by extreme muscle weakness and mental retardation. In DM2 the clinical phenotype is extremely variable and there are no distinct clinical subgroups. Congenital and childhood-onset forms are not present in DM2 and, in contrast to DM1, myotonia may be absent even on EMG. Due to the lack of awareness of the disease among clinicians, DM2 remains largely underdiagnosed. The delay in receiving the correct diagnosis after onset of first symptoms is very long in DM: on average more than 5 years for DM1 and more than 14 years for DM2 patients. The long delay in the diagnosis of DM causes unnecessary problems for the patients to manage their lives and anguish with uncertainty of prognosis and treatment

Basics for performing a high-quality color Doppler sonography of the vascular access

: In the last years, the systematic use of ultrasound mapping of the upper limb vascular network before the arteriovenous fistula (AVF) implantation, access maturation, and clinical management of late complications is widespread and expanding. Therefore, a good knowledge of theoretical outlines, instrumentation, and operative settings is undoubtedly required for a thorough examination. In this review, the essential Doppler parameters, B-Mode setting, and Doppler applications are considered. Basic concepts on the Doppler shift equation, angle correction, settings on pulse repetition frequency, operative Doppler frequency, gain are reported to ensure adequate and correct sampling of blood flow velocity. A brief analysis of the Doppler inherent artefacts (as random noise, blooming, aliasing, and motion artefacts) and the adjustment setting to minimize or eliminate the confounding artefacts are also considered. Doppler aliasing occurs when the pulse repetition frequency is set too low. This artefact is particularly frequent in vascular access sampling due to the high velocities range registered in the fistula's different segments. Aliasing should be recognized because its correction is crucial to analyse the Doppler signals correctly. Recent advances in instrumentation are also considered about a potential purchase of a portable ultrasound machine or a top-of-line, high-end, or mid-range ultrasound system. Last, the pulse wave Doppler setting for vascular access B-Mode and Doppler assessment is summarized

Muscle biopsy and cell cultures: potential diagnostic tools in hereditary skeletal muscle channelopathies.

Hereditary muscle channelopathies are caused by dominant mutations in the genes encoding for subunits of muscle voltage- gated ion channels. Point mutations on the human skeletal muscle Na+ channel (Nav1.4) give rise to hyperkalemic periodic paralysis, potassium aggravated myotonia, paramyotonia congenita and hypokalemic periodic paralysis type 2. Point mutations on the human skeletal muscle Ca2+ channel give rise to hypokalemic periodic paralysis and malignant hyperthermia. Point mutations in the human skeletal chloride channel ClC-1 give rise to myotonia congenita. Point mutations in the inwardly rectifying K+ channel Kir2.1 give rise to a syndrome characterized by periodic paralysis, severe cardiac arrhythmias and skeletal alterations (Andersen's syndrome). Involvement of the same ion channel can thus give rise to different phenotypes. In addition, the same mutation can lead to different phenotypes or similar phenotypes can be caused by different mutations on the same or on different channel subtypes. Bearing in mind, the complexity of this field, the growing number of potential channelopathies (such as the myotonic dystrophies), and the time and cost of the genetic procedures, before a biomolecular approach is addressed, it is mandatory to apply strict diagnostic protocols to screen the patients. In this study we propose a protocol to be applied in the diagnosis of the hereditary muscle channelopathies and we demonstrate that muscle biopsy studies and muscle cell cultures may significantly contribute towards the correct diagnosis of the channel involved. DNAbased diagnosis is now a reality for many of the channelopathies. This has obvious genetic counselling, prognostic and therapeutic implications

Ultrasound evaluation of access complications: Thrombosis, aneurysms, pseudoaneurysms and infections

: Arteriovenous fistula (AVF) complications are classified based on fistula outcomes. This review aims to update colour Doppler (CD) and pulse wave Doppler (PWD) roles in managing early and late complications of the native and prosthetic AVF. Vascular access (VA) failure occurs because inflow or outflow stenosis activates Wirchow's triad inducing thrombosis. Therefore, the diagnosis of the tributary artery and outgoing vein stenosis will be the first topic considered. Post-implantation complications occur from the inability to achieve AVF maturation and dialysis suitability due to inflow/outflow stenosis. Late stenosis is usually a sequence of early defects repaired to maintain patency. Less frequently, in the mature AVF or graft, complications are acquired 'de novo'. They derive either from incorrect management of vascular access (haematoma, pseudoaneurysm, prosthesis infection) or wall pathologies (aneurysm, myxoid valve degeneration, kinking, coiling, abnormal dilation from defects of elastic structures). High-resolution transducers (10-20 MHz) allow the characterization of the wall damage, haemodynamic dysfunctions, early and late complications even if phlebography remains the gold standard for the diagnosis for its sensitivity and specificity

Myotonic dystrophies : state of the art of new therapeutic developments for the CNS

Myotonic dystrophies are multisystemic diseases characterized not only by muscle and heart dysfunction but also by CNS alteration. They are now recognized as brain diseases affecting newborns and children for myotonic dystrophy type 1 and adults for both myotonic dystrophy type 1 and type 2. In the past two decades, much progress has been made in understanding the mechanisms underlying the DM symptoms allowing development of new molecular therapeutic tools with the ultimate aim of curing the disease. This review describes the state of the art for the characterization of CNS related symptoms, the development of molecular strategies to target the CNS as well as the available tools for screening and testing new possible treatments

Antennal arnpullary glands of Helicoverpa zea (Lepidoptera : Noctuidae)

In adult moths, the cephalic aorta terminates in an apical sack from which extends a pair of optic and antennal vessels that lie on either side of the esophagus, at the dorsoanterior surface of the brain. The base of each antennal vessel is dilated to form an ampulla that contains an oval mass of tissue, the antennal ampullary gland (AAG). An ultrastructural study revealed that the AAG of the corn earworm moth, Helicoverpa zea (Lepidoptera, Noctuidae), is composed of a single type of 40-50 parenchymal cells that produce secretory granules. The secretory material is released into the lymph channel of the ampullary vessel, suggesting that the AAG is an endocrine gland. Unlike the prothoracic gland and the corpus allatum, the AAG does not receive direct neural innervation; however, portions of the aortal muscle, associated with the ampullary wall, contain neurosecretory terminals and some of their products may also affect the AAG. No morphological differences were found between the AAG of males and females, with the exception that the glands in males were slightly larger. The function of the AAG remains unknown at this time. Because the AAG is located within the ampulla of the antennal vessel, one could assume that the product(s) of this gland may influence the response of the antennal sensory neurons to external stimuli