In Vivo DYSF Gene Viral Delivery Provides a Histoprotective Effect in Skeletal Muscle Tissue in Dysferlin-Deficient Mice.

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.

Morphofunctional Changes in the Spinal Cord of Rats after Contusion Injury with Local Delivery of Methylprednisolone in Combination with a Copolymer.

We studied the neuroprotective effect of local application of methylprednisolone in combination with a block copolymer after contusion spinal cord injury in rats. Histological analysis of the spinal cord showed that delivery of a complex of methylprednisolone with a block copolymer reduced the volume of white and gray matter lesions. An increase in the amplitude of the evoked response of the gastrocnemius muscle was observed during epidural stimulation of the spinal cord 6 h after the injury. The maximum amplitude of the muscle response was greater in the group with local delivery of the methylprednisolone complex with the polymer 72 h after the injury. The obtained results demonstrate the neuroprotective effect of the local administration of the complex and allow to make positive prognosis for the recovery of the sensorimotor functions in rats.

Structural and ultrastructural changes in the skeletal muscles of dysferlin-deficient mice during postnatal ontogenesis.

A number of sarcolemma proteins are responsible for muscle fiber repair. Dysferlin encoded by the DYSF gene is one of these proteins. Dysferlin promotes membrane repair in striated muscle fibers (MFs). Mutations in DYSF lead to loss of or decreased dysferlin expression, impaired membrane repair in MF, and its destruction, clinically manifesting as dysferlinopathy. Preclinical studies of cell and gene therapies aimed at restoring impaired muscle regeneration require well-characterized small animal models. Our investigation aimed to distinguish the histopathological features of a mouse strain lacking dysferlin expression (Bla/J strain). Ultrastructural changes in the sarcolemma, mitochondria and contractile apparatus were observed. It was shown that postnatal histogenesis of skeletal muscles in genetically determined dysferlin deficiency is characterized by a higher proportion of necrotic muscle fibers, compensatory hypertrophy of muscle fibers with their subsequent atrophy, and decreases in proliferative activity and the level of myogenic differentiation of myogenic progenitor cells compared to wild-type mice (C57Bl/6).

Reactive Changes in Elements of Stromal-Vascular Differons of Dysferlin-Deficient Skeletal Muscles after Procaine Injection.

The study assessed reactivity of stromal-vascular skeletal muscle differons to acute chemical injury. Dysferlin-deficient Bla/J mice and the wild-type С57BL/6 mice were intramuscularly injected with 100 µl of 0.5% procaine solution. The middle segment of gastrocnemius muscle was taken on postsurgery days 2, 4, 10, and 14 for routine histological examination. To evaluate proliferation and vascularization, the paraffin sections were stained immunohistochemically with antibodies to α-smooth muscle actin and Ki-67. The connective tissue was stained according to Mallory. The study revealed diminished proliferative activity of stromal-vascular differons and decreased vascular density in muscles of Bla/J mice. Thus, mutations in the DYSF gene coding dysferlin down-regulate the reparation processes in all differons of skeletal muscle.

[Recist 1.1 Criteria in the Assessment of Lung Tumors].

The paper considers the main provisions of the 2009 RECIST guidelines (version 1.1.) criteria for a standard approach to measuring lung tumor lesions and assessing the dynamics of the tumor process during treatment. This paper contains a list of conditions for carrying out multislice spiral computed tomography, under which the latter becomes maximally reproducible for the same patient, as well as an assessment of the course of the disease does optimal.