We studied the effects of a dual-vector DYSF gene delivery system based on adeno-associated virus serotype 9 capsids on pathological manifestations of dysferlinopathy in skeletal muscles of Bla/J mice lacking DYSF expression. The mice received intravenous injection of 3×1013 genomic copies of the virus containing the dual-vector system. M. gastrocnemius, m. psoas major, m. vastus lateralis, and m. gluteus superficialis were isolated for histological examination in 3, 6, and 12 weeks after treatment. Healthy wild-type (C57BL/6) mice served as positive control and were sacrificed 3 weeks after injection of 150 µl of 0.9% NaCl into the caudal vein. To detect dysferlin in muscle cryosections, immunohistochemical analysis with diagnostic antibodies was performed; paraffin sections were stained with hematoxylin and eosin for morphometric analysis. After administration of gene-therapeutic constructs, muscle fibers with membrane or cytoplasmic dysferlin location were detected in all examined muscles. The proportion of necrotic muscle fibers decreased, the number of muscle fibers with central location of the nucleus increased, and the mean cross-section area of the muscle fibers decreased.
Muscle, Skeletal , Muscular Dystrophies, Limb-Girdle , Mice , Animals , Dysferlin/genetics , Dysferlin/metabolism , Mice, Inbred C57BL , Muscle, Skeletal/metabolism , Muscular Dystrophies, Limb-Girdle/genetics , Muscular Dystrophies, Limb-Girdle/therapy , Muscular Dystrophies, Limb-Girdle/metabolism , Muscle Fibers, Skeletal/metabolism , Gene Transfer Techniques
The first documented case of mitochondrial neurogastrointestinal encephalomyopathy was described in 1962 by R. Luft. The variety and am-biguity of the clinical manifestations of the disease complicate its early diagnosis and treatment. The first clinical manifestations of the disease are associated with the pathology of the gastrointestinal tract. Low alertness and insufficient awareness of doctors delays the timely diagnosis of mitochondrial neurogastrointestinal encephalomyopathy. The aim of the work is to increase the alertness and awareness of narrow specialties about the possibility of differential diagnosis of an extremely rare detected disease on the base of our clinical observation.
Gastrointestinal Diseases , Intestinal Pseudo-Obstruction , Mitochondrial Encephalomyopathies , Ophthalmoplegia , Humans , Intestinal Pseudo-Obstruction/diagnosis , Intestinal Pseudo-Obstruction/etiology , Masks , Ophthalmoplegia/etiology , Ophthalmoplegia/complications , Mitochondrial Encephalomyopathies/diagnosis , Mitochondrial Encephalomyopathies/complications , Diagnosis, Differential , Rare Diseases/complications , Rare Diseases/diagnosis , Gastrointestinal Diseases/diagnosis
BACKGROUND: Patients with celiac disease present with not only gastrointestinal symptoms but also extraintestinal manifestations such as anemia, osteopathy, dermatitis herpetiformis, and celiac neuropathy. Despite a fairly wide range of celiac neuropathies, we report a case of the acrodystrophic variant of celiac polyneuropathy, which has not been previously described. CASE PRESENTATION: A 41-year-old Ukrainian male suffered from symmetric, sensorimotor axonal polyneuropathy and encephalopathy associated with celiac disease, which is characterized by severe trophic disorders in the lower extremities (trophic ulcers, hyperkeratosis, and anhidrosis). Acrodystrophic changes in the lower extremities were due to both neurogenic and direct immunoinflammatory damaging effects. Clinical-electrophysiological dissociation was also noted, which was represented by a gross axonal lesion with the preservation of muscle strength. The absence of enteropathic manifestations was accompanied by the pronounced histological changes in the duodenal mucosa by IIIb stage of Marsh. A gluten-free diet in combination with membrane plasma exchange and intravenous pulse methylprednisolone was prescribed to reduce the severity of sensory disorders and regression of encephalopathy within 7 months. CONCLUSION: Celiac disease may be a potential cause of neuropathy and encephalopathy in adult patients. Further immunosuppressive treatment protocols for both intestinal and extraintestinal manifestations of celiac disease are required.
Celiac Disease , Polyneuropathies , Adult , Celiac Disease/complications , Humans , Male , Polyneuropathies/etiology
UNLABELLED: Neurogenic copulative dysfunction (CD) is observed in different diseases and injuries of both the central and peripheral nervous system. CD concurrent with actual nervous system diseases has been established to be an important psychotraumatic factor that significantly reduces quality of life in these patients. AIM: To investigate the effect of aminophenylbutyric acid (Noophen) on male copulative function. SUBJECTS AND METHODS: Forty patients with chronic lumbosacral radiculopathy on an exacerbation and mild and moderate closed head injury were examined. RESULTS: The findings suggest that Noophen is effective in the combination therapy of neurogenic CD. CONCLUSION: The drug can normalize an autonomic control over nerve centers involved in the regulation of copulative function, and improve the psychoemotional status of patients.
Brain Injuries/complications , Nootropic Agents/pharmacology , Quality of Life/psychology , Radiculopathy/complications , Sexual Dysfunction, Physiological/drug therapy , Tranquilizing Agents/pharmacology , gamma-Aminobutyric Acid/analogs & derivatives , Adult , Diagnosis, Differential , Humans , Male , Middle Aged , Nootropic Agents/administration & dosage , Sexual Dysfunction, Physiological/diagnosis , Sexual Dysfunction, Physiological/etiology , Sexual Dysfunction, Physiological/physiopathology , Tranquilizing Agents/administration & dosage , Treatment Outcome , gamma-Aminobutyric Acid/administration & dosage , gamma-Aminobutyric Acid/pharmacology
Cholinergic system of mediation is the most prevalent in the human body. Acetylcholine provides interaction of neurons in the central nervous system and transmission of nerve impulses from the peripheral neurons to the effectors. The results of the recent studies have demonstrated the significance of cholinergic system dysfunction in development of different neurological diseases. Cholinesterase inhibitors are among the most common drugs used in treatment of this pathology. This review is dwelling upon the features of cholinesterase inhibitors and their practical application in treatment of the nervous system`s vascular pathology.
