Degeneration Of Fibers Research Articles

ACL Mucoid Degeneration—Anterior and Posterior Arthroscopic Decompression for Combined Knee Flexion-Extension Deficit

Mucoid degeneration of the ACL (MDACL, ACL ganglion cysts) is a disease involving ACL thickening due to accumulation of mucoid substance and fiber degeneration with possible formation of “ganglions”. Clinically, it leads to anteroposterior impingement and painful limitation of knee range of motion due to impingement of the anterior portion of the thickened ACL with the intercondylar notch during knee extension and the thickened posterior part of the ligament with posterior structures of the knee in flexion. Different treatment methods have been described, including total or partial resection of the ACL degenerative fibers. However, these techniques do not allow for ACL preservation and are associated with a risk of postoperative instability. Also, most procedures treat anterior impingement only. Therefore, the aim of this technical note is to present an arthroscopic technique allowing for minimally invasive anteroposterior ACL decompression. The technique is focused on evacuation of the interfibrous mucoid substance, ganglions, and bony decompression, as well as maintenance of ligament integrity. Its greatest advantage is that it is safe and ACL-preserving yet allows for comprehensive treatment of all intra- and extra-ligamentous possible reasons of MDACL origin and promoting good healing conditions.

Toxicologic Pathology Forum: Opinion on Interpretive Challenges for Procedure-Related Effects Associated With Direct Central Nervous System Delivery of Oligonucleotides to Rodents, Dogs, and Nonhuman Primates.

Direct delivery of therapeutics to the central nervous system (CNS) greatly expands opportunities to treat neurological diseases but is technically challenging. This opinion outlines principal technical aspects of direct CNS delivery via intracerebroventricular (ICV) or intrathecal (IT) injection to common nonclinical test species (rodents, dogs, and nonhuman primates) and describes procedure-related clinical and histopathological effects that confound interpretation of test article-related effects. Direct dosing is by ICV injection in mice due to their small body size, while other species are dosed IT in the lumbar cistern. The most frequent procedure-related functional effects are transient absence of lower spinal reflexes after IT injection or death soon after ICV dosing. Common procedure-related microscopic findings in all species include leukocyte infiltrates in CNS meninges or perivascular (Virchow-Robin) spaces; nerve fiber degeneration in the spinal cord white matter (especially dorsal and lateral tracts compressed by dosing needles or indwelling catheters), spinal nerve roots, and sciatic nerve; meningeal fibrosis at or near IT injection sites; hemorrhage; and gliosis. Findings typically are minimal to occasionally mild. Findings tend to be more severe and/or have a higher incidence in the spinal cord segments and spinal nerve roots at or close to the site of administration.

Alpha-Lipoic Acid, Palmitoylethanolamide, Myrrh, and Oxygen-Ozone Therapy Improve Pharmacological Therapy in Acute Painful Lumbosacral Radiculopathy due to Herniated Disc

BACKGROUND: Neuropathic mechanisms largely contribute to radicular Low Back Pain (LBP) and an increase in oxidative stress is recognized as one of the possible causes of nerve damage, inducing axonal degeneration and myelin degradation of nerve fibers. OBJECTIVES: We investigated whether a combination of nutraceutical supplements and oxygen-ozone (O2-O3) therapy might reduce disability and improve clinical effects of pharmacological therapy in patients with acute radicular LBP. STUDY DESIGN: This is a prospective, open-label, comparative observational study approved by the Institutional Review Board of the Sapienza University of Rome (RS 6285/2021). SETTING: Physical Medicine and Rehabilitation Unit of Sant’Andrea Hospital. METHODS: Within the scope of this study, 62 patients with acute radicular LBP diagnosed with disc herniation were assigned into 4 groups. The first group was assigned pharmacological therapy (n = 16), the second group was assigned pharmacological therapy and nutraceutical supplements (n = 15), the third group was assigned pharmacological therapy and O2-O3 therapy (n = 15), and the fourth group was assigned pharmacological therapy, nutraceutical supplements, and O2-O3therapy (n = 16). All patients who participated in the study were evaluated at the beginning of the study, 2 weeks, and 4 weeks (T2) after the beginning of treatment using the Numeric Rating Scale (NRS-11), Oswestry Disability Index (ODI), and 12-item Short-Form Health Survey. Opioid analgesic intake was noted from baseline to end of treatment (T2). RESULTS: In each group was observed a statistically significant difference for all measures compared to the baseline. At the T2 evaluation time between groups for the Mann-Whitney U test, a statistically significant difference was found: in the ODI scale between groups B and A (P = 0.004), groups C and A (P < 0.001), and groups D and A (P < 0.001); in the NRS-11 between groups B and A (P = 0.017), groups C and A (P = 0.002), and groups D and A (P < 0.001); in the 12-item Physical Component Summary score between groups B and A (P = 0.003), groups C and A (P = 0.002), and groups D and A (P < 0.001), while no significant differences between groups were observed in the 12-item Mental Component Summary score. The average days of opioid usage were similar in the 4 groups (8.33 in group A, 8.33 in group B, 8.33 in group C, and 8.75 in group D). However, the percentage of patients requiring adjuvant opioid therapy differed remarkably: 60% in group A, 40% in group B, 20% in group C, and 25% in group D. LIMITATIONS: A small number of patients were recruited, and we did not perform long-term follow-up. CONCLUSIONS: This study supports a multimodal approach combining nutraceutical supplements and O2-O3 therapy with pharmacological therapy in the treatment of acute radicular LBP secondary to disc herniation. The combination of neurotrophic and antioxidant therapies represents an etiopathogenetic approach, not purely symptomatic, that reduces symptomatology and avoids progression of the nerve damage. KEY WORDS: Low back pain, lumbar radicular pain, neuropathic pain, herniated disc, alpha lipoic acid, palmitoylethanolamide, myrrh, oxygen-ozone therapy, ozone, nutraceuticals

Swimming exercise attenuates mechanical hypersensitivity and mitigates peripheral nerve degeneration in rats with painful diabetic neuropathy (PDN)

BackgroundThis study aimed to assess the effectiveness of swimming exercise in alleviating mechanical hypersensitivity and peripheral nerve degeneration associated with a pre-clinical model of painful diabetic neuropathy (PDN). MethodsThis study is a pre-clinical study conducted using the streptozocin (STZ)-induced PDN rat model. Rats were randomly allocated to three groups: a vehicle group of non-diabetic rats (Vehicle, n = 9), a group of rats with PDN (PDN, n = 8), and a group of rats with PDN that performed a swimming exercise program (PDN-SW, n = 10). The swimming exercise program included daily 30-minute swimming exercise, 5 days per week for 4 weeks. Von Frey testing was used to monitor hindpaw mechanical sensitivity over 4 weeks. Assessment of cutaneous peripheral nerve fiber integrity was performed after the 4-week study period via immunohistochemistry for protein gene product 9.5-positive (PGP9.5+) intra-epidermal nerve fiber density (IENFD) in hind-paw skin biopsies by a blinded investigator. ResultsThe results showed that swimming exercise mitigated but did not fully reverse mechanical hypersensitivity in rats with PDN. Immunohistochemical testing revealed that the rats in the PDN-SW group retained higher PGP9.5+ IENFD compared to the PDN group but did not reach normal levels of the Vehicle group. ConclusionsThe results of this study indicate that swimming exercise can mitigate mechanical hypersensitivity and degeneration of peripheral nerve fibers in rats with experimental PDN.

Nucleoporin Seh1 maintains Schwann cell homeostasis by regulating genome stability and necroptosis

Schwann cells play critical roles in peripheral neuropathies; however, the regulatory mechanisms of their homeostasis remain largely unknown. Here, we show that nucleoporin Seh1, a component of nuclear pore complex, is important for Schwann cell homeostasis. Expression of Seh1 decreases as mice age. Loss of Seh1 leads to activated immune responses and cell necroptosis. Mice with depletion of Seh1 in Schwann cell lineage develop progressive reduction of Schwann cells in sciatic nerves, predominantly non-myelinating Schwann cells, followed by neural fiber degeneration and malfunction of the sensory and motor system. Mechanistically, Seh1 safeguards genome stability by mediating the interaction between SETDB1 and KAP1. The disrupted interaction after ablation of Seh1 derepresses endogenous retroviruses, which triggers ZBP1-dependent necroptosis in Schwann cells. Collectively, our results demonstrate that Seh1 is required for Schwann cell homeostasis by maintaining genome integrity and suggest that decrease of nucleoporins may participate in the pathogenesis of periphery neuropathies.

Chemical Synthesis, Safety and Efficacy of Antihypertensive Candidate Drug 221s (2,9)

Hypertension is the main risk factor of cardiovascular and cerebrovascular diseases. In this paper, a novel compound known as 221s (2,9), which includes tanshinol, borneol and a mother nucleus of ACEI, was synthesized by condensation esterification, deprotection, amidation, deprotection, and amidation, with borneol as the initial raw material, using the strategy of combinatorial molecular chemistry. The structure of the compound was confirmed by 1H NMR, 13C NMR, and high-resolution mass spectrometry, with a purity of more than 99.5%. The compound 221s (2,9) can significantly reduce the systolic and diastolic blood pressure of SHR rats by about 50 mmHg and 35 mmHg after 4 weeks of administration. The antihypertensive effect of 221s (2,9) is equivalent to that of captopril. The use of 221s (2,9) can reduce the content of Ren, Ang II and ACE in the serum of SHR rats, inhibit the RAAS and enhance the vascular endothelial function by upregulating the level of NO. Pathological studies in this area have shown that high dosage of 221s (2,9) can notably protect myocardial fibrosis in rats and reduce the degeneration and necrosis of myocardial fibers, inflammatory cell infiltration, and proliferation of fibrous tissue in the heart of rat. Therefore, the existing work provided a foundation for preclinical research and follow-up clinical research of 221s (2,9) as a new drug.

Increased IP3R-3 degradation induced by acrylamide promoted Ca2+-dependent calpain activation and axon damage in rats

Occupational and environmental exposure to acrylamide (ACR) can cause selective peripheral and central nerve fiber degeneration. IP3R-3 is an important transmembrane Ca2+ channel on the endoplasmic reticulum (ER), previous studies have found that ACR could induce Ca2+-dependent calpain activation and axon injury, but the exact role of IP3R-3 in ACR neuropathy is still unclear. Here we show that ACR exposure (40 mg/kg) markedly increased the ubiquitination of IP3R-3 in rat spinal cords, and promoted the degradation of IP3R-3 through the ubiquitin-proteasome pathway. Furthermore, the normal structure of ER, especially the mitochondrial associated membranes (MAMs) component, was significantly impaired in ACR neuropathy, and the ER stress pathway was activated, which indicated that the aberrant increase of cytoplasmic Ca2+ could be attributed the destruction of IP3R-3. Further investigation demonstrated that the proteasome inhibitor MG-132 effectively rescued the IP3R-3 loss, attenuated the intracellular Ca2+ increase, and reduced the axon loss of Neuron 2a (N2a) cells following ACR exposure. Moreover, the calpain inhibitor ALLN also reduced the loss of IP3R-3 and axon injury in N2a cells, but did not alleviate the Ca2+ increase in cytosol, supporting that the abnormal ubiquitination of IP3R-3 was the upstream of the cellular Ca2+ rise and axon damage in ACR neuropathy. Taken together, our results suggested that the aberrant IP3R-3 degradation played an important role in the disturbance of Ca2+ homeostasis and the downstream axon loss in ACR neuropathy, thus providing a potential therapeutic target for ACR neurotoxicity.

Fiber-specific age-related differences in the white matter of healthy adults uncovered by fixel-based analysis

Diffusion magnetic resonance imaging studies often investigate white matter (WM) microstructural degeneration in aging by probing WM regions that exhibit negative age associations of fractional anisotropy (FA). However, WM regions in which FA is unassociated with age are not necessarily “spared” in aging. Besides the confound of inter-participant heterogeneity, FA conflates all intravoxel fiber populations and does not allow the detection of individual fiber-specific age associations. In this study of 541 healthy adults aged 36–100 years, we use fixel-based analysis to investigate age associations among each “fixel” within a voxel, representing individual fiber populations. We find age associations of fixel-based measures that indicate age-related differences in individual fiber populations amid complex fiber architectures. Different crossing fiber populations exhibit different slopes of age associations. Our findings may provide evidence of selective degeneration of intravoxel WM fibers in aging, which does not necessarily manifest as a change in FA and therefore escapes notice if conventional voxel-based analyses are relied upon alone.

Patterns matter: differential effects of stress‐inducing and novelty‐associated locus coeruleus firing on pretangle tau pathophysiology in a rat model

AbstractBackgroundThe brainstem locus coeruleus (LC), the main source of brain norepinephrine (NE), is critically involved in several functions including wakefulness, vigilance, attention, learning and memory. LC functioning is firing pattern‐dependent. Phasic pattern promotes novelty and learning, while high tonic activity associates with stress and anxiety. LC has been identified as a key structure in Alzheimer’s disease (AD) development. Braak and colleagues propose that soluble abnormally phosphorylated tau (pretangle tau) originates in the LC early in life. The spreading of pretangle tau to other neuromodulatory areas and transentorhinal cortex constitutes Braak’s pretangle AD stages. Pretangle stages appear to be universal in human, however, only a portion of us develop AD. The selective vulnerability of individuals for AD is not understood. We hypothesized that differential LC activity patterns, influence the pretangle tau pathophysiology and the development of AD.MethodIn this study, an AAV carrying pseudo‐phosphorylated human tau (AAV9‐DIO‐EGFP‐htauE14) was infused into the LC of 2‐3 month‐old TH‐CRE rats, mimicking the onset of tauopathy during puberty in humans. Another AAV containing ChR2 opsin (AAVdj‐DIO‐ChR2‐mCherry) was co‐infused with htauE14. Chronic light stimulation of the LC of either a 10 Hz phasic pattern or a 25 Hz tonic pattern was carried out for 6 weeks. The performance of ChR2 rats in a battery of behavioral assays was compared with control groups without ChR2 (AAVdj‐DIO‐mCherry), 10 months following the AAV infusion. This was followed by immunohistochemistry and Western blotting comparing different biomarkers.ResultPhasic LC activation improved spatial and olfactory discrimination of the htauE14 rats, while chronic tonic activation increased stress level of the rats and led to anhedonia. Phasic pattern rescued axonal degeneration observed in the control htauE14 rats, showing higher density of LC fibers in the piriform cortex and hippocampal dentate gyrus. Tonic LC activation did not rescue LC fiber degeneration, instead, worsened LC neuronal health indexed by elevated level of active caspase 3. The learning performance was positively correlated with the LC fiber density.ConclusionThese results argue that variations in environmental experiences associated with differing LC activity patterns may account for individual susceptibility to development of AD in humans.

Scientific and Regulatory Policy Committee Points to Consider: Sampling, Processing, Evaluation, Interpretation, and Reporting of Test Article-Related Ganglion Pathology for Nonclinical Toxicity Studies.

Certain biopharmaceutical products consistently affect dorsal root ganglia, trigeminal ganglia, and/or autonomic ganglia. Product classes targeting ganglia include antineoplastic chemotherapeutics, adeno-associated virus-based gene therapies, antisense oligonucleotides, and anti-nerve growth factor agents. This article outlines "points to consider" for sample collection, processing, evaluation, interpretation, and reporting of ganglion findings; these points are consistent with published best practices for peripheral nervous system evaluation in nonclinical toxicity studies. Ganglion findings often occur as a combination of neuronal injury (e.g., degeneration, necrosis, and/or loss) and/or glial effects (e.g., increased satellite glial cell cellularity) with leukocyte accumulation (e.g., mononuclear cell infiltration or inflammation). Nerve fiber degeneration and/or glial reactions may be seen in nerves, dorsal spinal nerve roots, spinal cord, and occasionally brainstem. Interpretation of test article (TA)-associated effects may be confounded by incidental background changes or experimental procedure-related changes and limited historical control data. Reports should describe findings at these sites, any TA relationship, and the criteria used for assigning severity grades. Contextualizing adversity of ganglia findings can require a weight-of-evidence approach because morphologic changes of variable severity occur in ganglia but often are not accompanied by observable overt in-life functional alterations detectable by conventional behavioral and neurological testing techniques.

Next Generation Exon 51 Skipping Antisense Oligonucleotides for Duchenne Muscular Dystrophy.

In the last two decades, antisense oligonucleotides (AONs) that induce corrective exon skipping have matured as promising therapies aimed at tackling the dystrophin deficiency that underlies the severe and progressive muscle fiber degeneration in Duchenne muscular dystrophy (DMD) patients. Pioneering first generation exon 51 skipping AONs like drisapersen and eteplirsen have more recently been followed up by AONs for exons 53 and 45, with, to date, a total of four exon skipping AON drugs having reached (conditional) regulatory US Food and Drug Administration (FDA) approval for DMD. Nonetheless, considering the limited efficacy of these drugs, there is room for improvement. The aim of this study was to develop more efficient [2'-O-methyl-modified phosphorothioate (2'OMePS) RNA] AONs for DMD exon 51 skipping by implementing precision chemistry as well as identifying a more potent target binding site. More than a hundred AONs were screened in muscle cell cultures, followed by a selective comparison in the hDMD and hDMDdel52/mdx mouse models. Incorporation of 5-methylcytosine and position-specific locked nucleic acids in AONs targeting the drisapersen/eteplirsen binding site resulted in 15-fold higher exon 51 skipping levels compared to drisapersen in hDMDdel52/mdx mice. However, with similarly modified AONs targeting an alternative site in exon 51, 65-fold higher skipping levels were obtained, restoring dystrophin up to 30% of healthy control. Targeting both sites in exon 51 with a single AON further increased exon skipping (100-fold over drisapersen) and dystrophin (up to 40%) levels. These dystrophin levels allowed for normalization of creatine kinase (CK) and lactate dehydrogenase (LDH) levels, and improved motor function in hDMDdel52/mdx mice. As no major safety observation was obtained, the improved therapeutic index of these next generation AONs is encouraging for further (pre)clinical development.

Neurofilament Light Chain: A Translational Safety Biomarker for Drug-Induced Peripheral Neurotoxicity.

Branaplam is a splicing modulator previously under development as a therapeutic agent for Spinal Muscular Atrophy Type 1 and Huntington's disease. Branaplam increased the levels of survival motor neuron protein in preclinical studies and was well tolerated in early clinical studies; however, peripheral neurotoxicity was observed in a preclinical safety study in juvenile dogs. The aim of this study was to determine whether serum neurofilament light chain (NfL) concentrations in dogs could serve as a monitoring biomarker for branaplam-induced peripheral neurotoxicity. A 30-week time-course investigative study in dogs treated with vehicle control (negative control), neurotoxic pyridoxine (positive control), or branaplam was conducted to assess neuropathology, nerve morphometry, electrophysiological measurements, gene expression profiles, and correlation to NfL serum concentrations. In branaplam-treated animals, a mild to moderate nerve fiber degeneration was observed in peripheral nerves correlating with increased serum NfL concentrations, but there were no observed signs or changes in electrophysiological parameters. Dogs with pyridoxine-induced peripheral axonal degeneration displayed clinical signs and electrophysiological changes in addition to elevated serum NfL. This study suggests that NfL may be useful as an exploratory biomarker to assist in detecting and monitoring treatment-related peripheral nerve injury, with or without clinical signs, associated with administration of branaplam and other compounds bearing a neurotoxic risk.

Immune activity of Ki-67 during nasal polyp development.

Nasal polyps are non-cancerous, soft painless growth of nasal mucosa. In this study, our aim was to investigate the Ki-67 expression level in nasal polyps by immunohistochemical method. 30 patients with nasal polyps were included in this study. Nasal polyps were processed for paraffin wax embedding protocol. Samples were fixed and embedded in paraffin blocks. 5 µm sections were stained with Hematoxylin-Eosin dye and immune stained with Ki-67 antibody. Sections were analyzed under light microscope. Blood parameters showed that white blood cells, hematocrit and platelet were higher than normal range. In sections of hematoxylin-eosin staining, elevated basal cells, thin basement membrane, leukocyte infiltration, collagen fibers degeneration were observed. Masson trichrome staining revealed that degenerative epithelial cells, detached basement membrane and edema were observed. Ki-67 expression was observed in mucosal epithelial cells, vascular endothelial cells and plasma cells in immune staining. Epithelial degeneration in nasal polyps and leukocyte infiltration induce nasal adenoma. Ki-67 expression may be a diagnostic tool for epithelial leukocyte formation.

Roles of miR-196a and miR-196b in Zebrafish Motor Function.

The exertion of motor function depends on various tissues, such as bones and muscles. miR-196 has been widely studied in cancer and other fields, but its effect on bone and skeletal muscle is rarely reported. In order to explore the role of miR-196 family in bone and skeletal muscle, we used the previously successfully constructed miR-196a-1 and miR-196b gene knockout zebrafish animal models for research. The behavioral trajectories of zebrafish from 4 days post-fertilization (dpf) to 7 dpf were detected to analyze the effect of miR-196a-1 and miR-196b on motor ability. Hematoxylin-eosin (HE) staining and transmission electron microscopy (TEM) were used to detect the dorsal muscle tissue of zebrafish. The bone tissue of zebrafish was detected by microcomputed tomography (micro-CT). Real-time PCR was used to detect the expression levels of related genes, including vcp, dpm1, acta1b, mylpfb, col1a1a, bmp8a, gdf6a, and fgfr3. The behavioral test showed that the total behavioral trajectory, movement time, and movement speed of zebrafish larvae were decreased in the miR-196a-1 and miR-196b gene knockout lines. Muscle tissue analysis showed that the structure of muscle fibers in the zebrafish lacking miR-196a-1 and miR-196b was abnormal and was characterized by vacuolar degeneration of muscle fibers, intranuclear migration, melanin deposition, and inflammatory cell infiltration. Bone CT examination revealed decreased bone mineral density and trabecular bone number. The real-time PCR results showed that the expression levels of vcp, dpm1, gdf6a, fgfr3, and col1a1a were decreased in the miR-196b gene knockout group. The expression levels of dpm1, acta1b, mylpfb, gdf6a, and col1a1a were decreased, and the expression level of fgfr3 was increased in the miR-196b gene knockout group compared with the wild-type group. miR-196a-1 and miR-196b play an important role in muscle fiber structure, bone mineral density, and bone trabecular quantity by affecting the expression of vcp, dpm1, acta1b, mylpfb, gdf6a, fgfr3, and col1a1a and then affect the function of the motor system.

A computational model to simulate spectral modulation and speech perception experiments of cochlear implant users.

Speech understanding in cochlear implant (CI) users presents large intersubject variability that may be related to different aspects of the peripheral auditory system, such as the electrode-nerve interface and neural health conditions. This variability makes it more challenging to proof differences in performance between different CI sound coding strategies in regular clinical studies, nevertheless, computational models can be helpful to assess the speech performance of CI users in an environment where all these physiological aspects can be controlled. In this study, differences in performance between three variants of the HiRes Fidelity 120 (F120) sound coding strategy are studied with a computational model. The computational model consists of (i) a processing stage with the sound coding strategy, (ii) a three-dimensional electrode-nerve interface that accounts for auditory nerve fiber (ANF) degeneration, (iii) a population of phenomenological ANF models, and (iv) a feature extractor algorithm to obtain the internal representation (IR) of the neural activity. As the back-end, the simulation framework for auditory discrimination experiments (FADE) was chosen. Two experiments relevant to speech understanding were performed: one related to spectral modulation threshold (SMT), and the other one related to speech reception threshold (SRT). These experiments included three different neural health conditions (healthy ANFs, and moderate and severe ANF degeneration). The F120 was configured to use sequential stimulation (F120-S), and simultaneous stimulation with two (F120-P) and three (F120-T) simultaneously active channels. Simultaneous stimulation causes electric interaction that smears the spectrotemporal information transmitted to the ANFs, and it has been hypothesized to lead to even worse information transmission in poor neural health conditions. In general, worse neural health conditions led to worse predicted performance; nevertheless, the detriment was small compared to clinical data. Results in SRT experiments indicated that performance with simultaneous stimulation, especially F120-T, were more affected by neural degeneration than with sequential stimulation. Results in SMT experiments showed no significant difference in performance. Although the proposed model in its current state is able to perform SMT and SRT experiments, it is not reliable to predict real CI users' performance yet. Nevertheless, improvements related to the ANF model, feature extraction, and predictor algorithm are discussed.

Histopathological and immunohistochemical study to determine the effects of monosodium glutamate on skeletal muscle development in chickens

The aim of this report was to investigate the effects of MSG administration on embryonic skeletal muscle development in chickens, using histological, histopathological, and immunohistochemical methods. A total of 410 fertilized chicken eggs were used and were divided into five groups: negative control, vehicle control, low-dose group (0.12 mg/g egg MSG), medium-dose group (0.6 mg/g egg MSG), and high-dose group (1.2 mg/g egg MSG). At incubation days 15, 18, and 21, eggs from each group were opened and six live embryos were obtained. The embryos were sacrificed by decapitation, and skeletal muscle tissue samples (musculus fibularis longus and musculus sternocoracoideus pectoralis) were obtained. Sections were stained with hematoxylin-eosin. Moreover, caspase-3 reactivity was determined using the immunohistochemical method. As a result, muscle development was delayed in the MSG groups and the number of caspase-3-positive cells was higher (p < 0.05) than in the controls. Histopathological examinations revealed degenerative and necrotic changes in the skeletal muscle. Muscle degeneration (edema, muscle fiber degeneration, Zenker’s necrosis, and mononuclear cell infiltrations) were observed in all groups, except for the control groups. It was concluded that MSG may have adversely affected the development of the skeletal muscle.

Crouzon syndrome complicated with binocular strabismus and extraocular muscle fibrosis: a case report

BackgroundCrouzon syndrome, a rare genetic disorder characterized by premature closure of coronal sutures, results in skull and facial deformities along with abnormal brain and ocular development.Case presentationHere, we report a case of a 27-year-old ethnic han male patient who presented with complex binocular strabismus secondary to Crouzon syndrome. At the time of surgery, extraocular muscles were found to be fibrotic and results of the pathological examination revealed degeneration of muscle fibers, which were replaced by adipose tissue. The entire exome sequencing DNA testing indicated that the patient and his father possessed the fibroblast growth factor receptor 2 (FGFR2) gene c.G812T:p.G271V heterozygous mutation. Binocular strabismus corrective surgery was performed in this patient with a satisfactory outcome.ConclusionsThis case demonstrates that Crouzon syndrome patients can show an FGFR2 gene c.G812T:p.G271V mutation and display clinical symptoms such as extraocular muscle fibrosis, exotropia, exophthalmos, and a pointed head deformity.

Tricaprin can prevent the development of AAA by attenuating aortic degeneration

Medical therapeutic options to prevent rupture of abdominal aortic aneurysm (AAA), a critical event, must be developed. Moreover, further understanding of the process of AAA development and rupture is crucial. Previous studies have revealed that aortic hypoperfusion can induce the development of AAA, and we successfully developed a hypoperfusion-induced AAA animal model. In this study, we examined the effects of medium-chain triglycerides (MCTs), tricaprylin (C8-TG) and tricaprin (C10-TG), on hypoperfusion-induced AAA rat model. We estimated the effects of MCTs on aortic pathologies, mechanical properties of the aorta, and development of AAA. C10-TG, but not C8-TG, significantly suppressed AAA development and completely prevented the rupture. We observed that C10-TG prevented the development and rupture of AAA, but not C8-TG. Additionally, regression of AAA diameter was observed in the C10-TG group. Pathological analysis revealed C10-TG improved the hypoperfusion-induced increase in hypoxia-inducible factor-1α levels, medial smooth muscle cells (SMCs) loss, degeneration of aortic elastin and collagen fibers, and loss of aortic wall elasticity. In addition, regression of the formed AAA was observed by administration of C10-TG after AAA formation. C10-TG administration after AAA formation improved degeneration of AAA wall including degradation of aortic elastin and collagen fibers, stenosis of vasa vasorum, and loss of medial SMCs. These data suggest C10-TG can prevent AAA by attenuating aortic hypoperfusion and degeneration. Considering the clinical safety of C10-TG, C10-TG can be a promising AAA drug candidate.

Морфологическое исследование процессов валлеровской дегенерации в седалищном нерве крысы после механического повреждения

Introduction. Peripheral nerve injury is an important social problem. Fundamental research on mechanisms regulating degenerative and reparative processes that occur in the nerve following injury is necessary to find new ways of improving nerve regeneration. The purpose was to study the structural changes in the distal segment of the rat sciatic nerve at early stages following injury (ligature) using immunohistochemical and histochemical methods. Materials and methods. The rat sciatic nerve was subjected to mechanical trauma through ligation for a duration of 40 seconds. After days 7, 21, and 60, we analyzed changes in the nerve fibers using immunohistochemical reactions for alpha-tubulin and Luxol Fast Blue stains for myelin. Antibodies to tight junction protein claudin-1 were used to study perineurial cells. We identified Schwann cells (neurolemmocytes) and macrophages with the reaction for GFAP and the Iba-1 protein IHC reaction, respectively. Results. After 7 days, we observed degeneration of most nerve fibers, disintegration of myelin sheaths, disruption of the blood-neural barrier, migration of hematogenous macrophages, and dedifferentiation of Schwann cells in the endoneurium of the rat sciatic nerve distal segment. However, after day 21, the growth of nerve fibers from the proximal segment of the nerve and their remyelination were observed. The density of nerve fibers reached its highest value 60 days after the injury. Conclusion. We evaluated the relationship between the degree of myelin breakdown and the number of Iba-1+ macrophages, detected changes in the perineurium in the distal segment of the nerve, and identified dedifferentiated mitotically dividing Schwann cells. Keywords: Wallerian degeneration, damaged rat nerve, Luxol Fast Blue, claudin-1, Iba-1 protein, GFAP, immunohistochemistry

Epizootological data of cattle infection caused by bacillus cereus on a dairy farm of the Kemerovo region

Diseases caused by Bacillus cereus of non-food origin are becoming relevant. This article describes a case of an epizootic situation associated with the spread of B. cereus through cattle feed and its ubiquitous distribution to all environmental objects and animal biotopes on the farm. B. cereus can cause not only food poisoning but also a generalized form of the infectious process, characterized by severe intestinal stagnation with a thickened and edematous wall, hemorrhages on the mucosal surface, catarrhal enteritis, systemic lymphadenopathy, degeneration of muscle fibers, interstitial pneumonia with pulmonary edema and pericardial effusion, meningeal and splenic hyperemia, glomerulonephritis and renal liver failure. Bacillus cereus was the predominant microorganism in quantitative terms with the specified pathoanatomical picture. Microorganisms of the Enterococcuscea, Staphylococcuscea families were found together with B. cereus. B. cereus was found in biological material (cervical mucus, nasal discharge) from live animals and in environmental objects. The removal of contaminated feed from the diet of animals led to a decrease in the death of livestock. It was concluded based on this that the main factor in the transmission of the pathogen was the food supply.