Necrotic Fibers Research Articles

Immunopathological Characterization of Muscle Biopsy Samples from Immune-Mediated Necrotizing Myopathy Patients.

BackgroundImmune-mediated necrotizing myopathy (IMNM) is a relatively new proposed category of idiopathic inflammatory myopathies (IIMs), characterized by the presence of abundant necrotic muscle fibers, myophagocytosis, and sparse inflammatory infiltrates. The aim of our study was to analyze the immunopathological characteristics of IMNM by detecting biopsy samples from a cohort of patients, and to delineate the pathways involved in the pathogenesis.Material/MethodsA retrospective evaluation of muscle biopsy samples, clinical and laboratory data, and immunohistochemical analysis of macrophages MHC-I and MAC, was performed for all patients diagnosed as having IMNM but without a prior exposure to statins.ResultsImmunohistochemical analysis revealed the presence of CD68+ macrophages mainly in the necrotic muscle fibers and the endomysial connective tissue. MHC-I and MAC positively stained not only the necrotic fibers or vessels but also the non-necrotic ones.ConclusionsOur data describe general immunological features in IMNM patients, which may be helpful in serving as biomarkers, aid in diagnostic decisions, and provide clues into the underlying mechanisms involved in this disease.

The Effect of the Wooden Breast Myopathy on Sarcomere Structure and Organization.

The wooden breast (WB) has been classically identified by the phenotypic presence of a wood-like pectoralis major (p. major) muscle. The WB-affected p. major muscle is characterized by necrotic muscle fibers and the replacement of muscle with connective tissue, water, and fat. The objective of the current study was to determine the effect of the WB myopathy on sarcomere organization by transmission electron microscopy. Sarcomere structure and organization were examined in two broiler lines with a high incidence of WB (Lines A and B) and another broiler line without WB (Line C). Affected muscle had an increase in smaller myofibers with diameters of 20 μm or less. Sarcomere organization decreased with fiber diameter in both Lines A and B. The structure and organization of sarcomeres in Line C were similar to WB-unaffected muscle in Lines A and B. Taken together, these data demonstrate that the WB myopathy detrimentally affects sarcomere organization in a broiler line-specific manner. Disorganization of sarcomere structure will affect the function of the p. major muscle as well as meat quality.

Necrosis in anti-SRP+ and anti-HMGCR+myopathies: Role of autoantibodies and complement.

To characterize muscle fiber necrosis in immune-mediated necrotizing myopathies (IMNM) with anti-signal recognition particle (SRP) or anti-3-hydroxy-3-methylglutarylcoenzyme A reductase (HMGCR) antibodies and to explore its underlying molecular immune mechanisms. Muscle biopsies from patients with IMNM were analyzed and compared to biopsies from control patients with myositis. In addition to immunostaining and reverse transcription PCR on muscle samples, in vitro immunostaining on primary muscle cells was performed. Creatine kinase levels and muscle regeneration correlated with the proportion of necrotic fibers (r = 0.6, p < 0.001). CD68+iNOS+ macrophages and a Th-1 immune environment were chiefly involved in ongoing myophagocytosis of necrotic fibers. T-cell densities correlated with necrosis but no signs of cytotoxicity were detected. Activation of the classical pathway of the complement cascade, accompanied by deposition of sarcolemmal immunoglobulins, featured involvement of humoral immunity. Presence of SRP and HMGCR proteins on altered myofibers was reproduced on myotubes exposed to purified patient-derived autoantibodies. Finally, a correlation between sarcolemmal complement deposits and fiber necrosis was observed (r = 0.4 and p = 0.004). Based on these observations, we propose to update the pathologic criteria of IMNM. These data further corroborate the pathogenic role of anti-SRP and anti-HMGCR autoantibodies in IMNM, highlighting humoral mechanisms as key players in immunity and myofiber necrosis.

Necrotizing autoimmune myopathy: Muscle weakness due to atorvastatin

Statins are medications with great use. One of the side effects of medications is myopathy. In some case, statins switch on, a process of autoimmune system which will not terminate with discontinuation of statins. Necrotizing autoimmune myopathy (NAM) is a subgroup of inflammatory myopathies characterized pathologically by necrotic muscle fibers with absent or minimal inflammation. The purpose of this study was to describe NAM in a patient undergoing treatment with atorvastatin for an extended period, diagnosis of the disease process, treatment, and resolution of symptoms. The case presented in this paper is about 72-year-old woman who showed continued general weakness even though she stopped taking atorvastatin. This patient also had elevated creatine kinase and aldolase. Myopathy confirmed by muscle biopsy. She was treated with intravenous immune globulin (IVIG) and pulse of methyl prednisolone and followed with high dose of steroid and azathioprine. Our case report illustrates the importance of early recognition of NAM and that the treatment with immediately administer IVIG, pulse of methylprednisolone, and high dose of steroid can result in complete recovery.

Bilateral muscle fiber and nerve influences by TNF-alpha in response to unilateral muscle overuse \u2013 studies on TNF receptor expressions

BackgroundTNF-alpha is suggested to be involved in muscle damage and muscle inflammation (myositis). In order to evaluate whether TNF-alpha is involved in the myositis that occurs in response to muscle overuse, the aim was to examine the expression patterns of TNF receptors in this condition.MethodsA rabbit muscle overuse model leading to myositis in the soleus muscle was used. The expression patterns of the two TNF receptors Tumor Necrosis Factor Receptor type 1 (TNFR1) and Tumor Necrosis Factor Receptor type 2 (TNFR2) were investigated. In situ hybridization and immunofluorescence were utilized. Immunostainings for desmin, NK-1R and CD31 were made in parallel.ResultsImmunoreactions (IR) for TNF receptors were clearly observed in white blood cells, fibroblasts and vessel walls, and most interestingly also in muscle fibers and nerve fascicles in the myositis muscles. There were very restricted reactions for these in the muscles of controls. The upregulation of TNF receptors was for all types of structures seen for both the experimental side and the contralateral nonexperimental side. TNF receptor expressing muscle fibers were present in myositis muscles. They can be related to attempts for reparation/regeneration, as evidenced from results of parallel stainings. Necrotic muscle fibers displayed TNFR1 mRNA and TNFR2 immunoreaction (IR) in the invading white blood cells. In myositis muscles, TNFR1 IR was observed in both axons and Schwann cells while TNFR2 IR was observed in Schwann cells. Such observations were very rarely made for control animals.ConclusionsThe findings suggest that there is a pronounced involvement of TNF-alpha in the developing myositis process. Attempts for reparation of the muscle tissue seem to occur via both TNFR1 and TNFR2. As the myositis process also occurs in the nonexperimental side and as TNF receptors are confined to nerve fascicles bilaterally it can be asked whether TNF-alpha is involved in the spreading of the myositis process to the contralateral side via the nervous system. Taken together, the study shows that TNF-alpha is not only associated with the inflammation process but that both the muscular and nervous systems are affected and that this occurs both on experimental and nonexperimental sides.

Irreversible electroporation of the uterine cervix in a rabbit model.

The aim of this study was to evaluate the effects of irreversible electroporation (IRE) on the uterine cervix in a rabbit model. IRE ablation was performed in the cervices of 48 New Zealand rabbits, with one ablation lesion in each animal. Gross pathology, transmission electron microscopy, hematoxylin and eosin (H&E), Masson's trichrome (MT) stain, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays were performed at pre-set time points (0h, 12h, 1 d, 2 d, 4 d, 7 d, 14 d, and 28 d post-IRE). All the rabbits tolerated the IRE ablation without serious complications. IRE caused complete cell death of the ablated cervix via cell apoptosis. However, fast recovery of the cervix was observed from 7 d post-IRE, with the signs of collagen fibers hyperplasia, the disappearance of the necrotic cells and muscle fibers, and regeneration and extension of the cervical epithelium. At 28 d post-IRE, the ablated cervices recovered to almost normal. Our study suggested that IRE might be an efficient and safe technology to treat cervical tumors, without causing serious cervical damage.

Effective induction therapy for anti-SRP associated myositis in childhood: A small case series and review of the literature

BackgroundAnti-Signal Recognition Particle associated myopathy is a clinically and histopathologically distinct subgroup of Juvenile Idiopathic Inflammatory Myositis, which is under-recognised in children and fails to respond to conventional first line therapies. We present three cases where remission was successfully induced using combination therapy with intensive rehabilitation.Case presentationsThree new patients are reported. All 3 cases presented with profound, rapid-onset, proximal myopathy and markedly raised CK, but no rash. Histology revealed a destructive myopathy characterized by scattered atrophic and necrotic fibres with little or no inflammatory infiltrate. All 3 patients responded to induction with cyclophosphamide, IVIG and rituximab, in conjunction with intensive physiotherapy and methotrexate as the maintenance agent. Our patients regained near-normal strength (MMT > 70/80), in contrast with the current literature where >50% of cases reported severe residual weakness.A literature search on paediatric anti-SRP myositis was performed to June 2016; PubMed was screened using a combination of the following terms: signal recognition particle, autoantibodies, antibodies, myositis, muscular diseases, skeletal muscle, childhood, paediatric, juvenile. Articles in a foreign language were excluded. Nine case studies were found.ConclusionThis paper supports the hypothesis that anti-SRP myositis is distinct from other JIIM. It is an important differential to JDM and should be considered where there is severe weakness without rash or if highly elevated muscle enzymes (CK > 10,000 U/l) are found. Early identification is essential to initiate aggressive medical and physical therapy. Greater international collaboration and long-term follow-up data is needed to establish the most effective treatment strategy for this rare group of patients.

Granulomatous Necrotizing Myositis in Swine Affected by Porcine Circovirus Disease.

Porcine circovirus type 2 (PCV2) is associated with multiple clinical syndromes in pigs, known as porcine circovirus diseases. This work describes an outbreak of porcine circovirus diseases with severe lesions affecting the skeletal muscle. Ninety-two pigs had apathy, weight loss, and diarrhea over a clinical course of 7 to 10 days. Approximately 30 of the pigs had stiff gait, muscle weakness, hind limb paresis, and recumbency. Twelve of the 92 pigs were necropsied, and 4 had pale discoloration of skeletal muscles with microscopic lesions of granulomatous necrotizing myositis. Immunohistochemistry of skeletal muscle showed that PCV2 antigen was located primarily in the cytoplasm and nuclei of macrophages, lymphocytes, and multinucleated giant cells, with a lower amount in the cytoplasm of endothelial cells, necrotic fibers, and satellite cells. Affected muscle samples were polymerase chain reaction-positive for PCV2 and the amplicon exhibited 99% identity with sequences belonging to the PCV2b genotype. Locomotor clinical signs and granulomatous necrotizing myositis should be considered as another expression of PCV2 infection in pigs.

Flexible Nanoholey Patches for Antibiotic-Free Treatments of Skin Infections.

Despite the availability of different antibiotics, bacterial infections are still one of the leading causes of hospitalization and mortality. The clinical failure of antibiotic treatment is due to a general poor antibiotic penetration to bacterial infection sites as well as the development of antibiotic-resistant pathogens. In the case of skin infection, the wound is covered by exudate, making it impermeable to topical antibiotics. The development of a flexible patch allowing a rapid and highly efficient treatment of subcutaneous wound infections via photothermal irradiation is presented here. The skin patch combines the near-infrared photothermal properties of a gold nanohole array formed by self-assembly of colloidal structures on flexible polyimide films with that of reduced graphene oxide nanosheets for laser-gated pathogen inactivation. In vivo tests performed on mice with subcutaneous skin infection and treated with the photothermal skin patch show wound healing of the infected site, while nontreated areas result in necrotic muscular fibers and bacterial infiltrate. No loss in efficiency is observed upon multiple use of these patches during in vivo experiments because of their robustness.

P.185 - First case report of Nivolumab-induced dermatomyositis

Adverse effects of immune checkpoints inhibitors such as nivolumab include various autoimmune disorders, although myositis is rare in this context. To report a biopsy-proven case of dermatomyositis in a patient treated with nivolumab. The patient's medical history, clinical and ancillary findings and early outcome are reported. A 79 year-old male patient developed head drop, bulbar symptoms, dyspnea, and quadriparesis with diffuse amyotrophy and areflexia 3 weeks after initiation of nivolumab therapy for a relapsing lung adenocarcinoma. Serum creatine kinase were increased at 2 450 UI/L (N < 200). Anti-AChR antibodies and myositis-associated were undetectable. Echocardiography, cerebrospinal fluid analysis and brain and spine MRI were unremarkable. Functional respiratory explorations displayed a severe restrictive syndrome. Electromyography revealed fibrillation potential in upper cervical muscles, right trapezius, and both tibialis anterior, with normal nerve conduction and single-fiber studies. Left deltoid biopsy displayed features of dermatomyositis, including fascicular necrotising fibers, perifascicular atrophy and HLA-I membranous positivity, C5B9 expression by 1 necrotic fiber and thin complement deposits in few capillaries; no vascularitis was observed. Nivolumab was discontinued and steroids and monthly intravenous immunoglobulins were initiated. Partial improvement was observed 2 months after onset. We report the first documented case of dermatomyositis in a patient under nivolumab therapy. Discontinuation of nivolumab and treatment with steroids and intravenous immunoglobulins appeared beneficial.

Platelet-Derived Growth Factor BB Influences Muscle Regeneration in Duchenne Muscle Dystrophy

Duchenne muscular dystrophy (DMD) is characterized by a progressive loss of muscle fibers, and their substitution by fibrotic and adipose tissue. Many factors contribute to this process, but the molecular pathways related to regeneration and degeneration of muscle are not completely known. Platelet-derived growth factor (PDGF)-BB belongs to a family of growth factors that regulate proliferation, migration, and differentiation of mesenchymal cells. The role of PDGF-BB in muscle regeneration in humans has not been studied. We analyzed the expression of PDGF-BB in muscle biopsy samples from controls and patients with DMD. We performed invitro experiments to understand the effects of PDGF-BB on myoblasts involved in the pathophysiology of muscular dystrophies and confirmed our results invivo by treating the mdx murine model of DMD with repeated i.m. injections of PDGF-BB. We observed that regenerating and necrotic muscle fibers in muscle biopsy samples from DMD patients expressed PDGF-BB. Invitro, PDGF-BB attracted myoblasts and activated their proliferation. Analysis of muscles from the animals treated with PDGF-BB showed an increased population of satellite cells and an increase in the number of regenerative fibers, with a reduction in inflammatory infiltrates, compared with those in vehicle-treated mice. Based on our results, PDGF-BB may play a protective role in muscular dystrophies by enhancing muscle regeneration through activation of satellite cell proliferation and migration.

Novel mutation (c.8725T&gt;C) in two siblings with late-onset LAMA2-related muscular dystrophy

Objective: LAMA2 mutation-related muscular dystrophy is classified into two clinical phenotypes: severe early-onset congenital muscular dystrophy and mild late- onset muscular dystrophy. According to several reported cases, late-onset LAMA2-related muscular dystrophy clinically shows the limb girdle muscular dystrophy pattern and has been considered to be associated with the partial expression of laminin α2. Methods: We describe here a patient initially suspected of having limb girdle muscular dystrophy, but was later diagnosed with late-onset LAMA2-related muscular dystrophy. Results: We found compound heterozygous variations on the patient's LAMA2 gene, a heterozygous nonsense variation in exon 49 (c.6955C>T/p.Arg2319*), previously reported as a pathogenic variation, and a heterozygous missense variation in exon 62 (c.8725T>C/p.Cys2909Arg), which is a novel variation. Her and her sister's brain magnetic resonance images (MRI) revealed diffuse symmetric high signal unmyelinated changes in bilateral cerebral white matter. Muscle tissue sections were stained with hematoxylin and eosin, and showed mild muscle fiber size variation, a few necrotic and regenerative muscle fibers, and endomysial edema Immunohistochemical staining for laminin α2 showed a reduction compared with the control. Conclusion: We suggest that this novel missense mutation is the likely pathogenic mechanism through the genotype–phenotype correlation and the annotation process.

Integrated Diagnosis Project for Inflammatory Myopathies: An association between autoantibodies and muscle pathology.

Inflammatory myopathies are a heterogeneous group of immune-mediated diseases that involve skeletal muscle as well as many other organs. The classification of inflammatory myopathies has been based on clinical diagnoses, pathological diagnoses, and autoantibodies, independently. The clinical phenotypes of inflammatory myopathies are characterized by various autoantibodies that are originally detected by RNA or protein immunoprecipitation. However, since the correlation between histological features and autoantibodies had not been fully elucidated, we created the "Integrated Diagnosis Project for Inflammatory Myopathies" in October 2010. Based on our work and previous studies, the three major subsets of inflammatory myopathies defined by autoantibodies are immune-mediated necrotizing myopathy (IMNM), antisynthetase syndrome, and dermatomyositis. IMNM is the pathological entity, characterized by significant necrotic and regeneration muscle fibers with minimal or no inflammatory cell infiltration. The detection of autoantibodies against signal recognition particles or 3-hydroxy-3-methylglutaryl-coenzyme A reductase is important for the diagnosis of IMNM. Antisynthetase syndrome, characterized by myositis, interstitial lung disease, skin rash, arthropathy, and Raynaud phenomenon, is the clinical entity based on the presence of aminoacyl transfer RNA synthetase antibodies. Perifascicular necrosis is a distinctive hallmark of antisynthetase syndrome in muscle pathology. The diagnosis of dermatomyositis is usually based on clinical features of typical skin rash. Several autoantibodies are associated with specific subsets of dermatomyositis. Myxovirus resistance A expression in the myofiber cytoplasm has a better sensitivity for the diagnosis of dermatomyositis compared to perifascicular atrophy. The screening of autoantibodies has clinical relevance for managing patients with inflammatory myopathies.

Anti-HMGCR Autoantibodies in Juvenile Idiopathic Inflammatory Myopathies Identify a Rare but Clinically Important Subset of Patients.

We aimed to establish the prevalence and clinical associations of anti-HMG-CoA-reductase (anti-HMGCR) in a large UK cohort with juvenile myositis. There were 381 patients investigated for anti-HMGCR using ELISA. Anti-HMGCR autoantibodies were detected in 4 patients (1%). These children had no or minimal rash and significant muscle disease. Muscle biopsies were considered distinctive, with widespread variation in fiber size, necrotic fibers, and chronic inflammatory cell infiltrates; all had prolonged elevation of creatine kinase and all ultimately received biologic therapies. Anti-HMGCR in UK children with myositis are associated with severe disease that is poorly responsive to standard treatment.

Molecular Recognition Mechanism of Hematopoietic Prostaglandin D Synthase with its Cofactor and Substrate

Hematopoietic prostaglandin (PG) D synthase (H-PGDS) is a Sigma class member of the glutathione S-transferase (GST) superfamily, and requires glutathione (GSH) as a cofactor. H-PGDS catalyzes the isomerization of prostaglandin H2 (PGH2) to prostaglandin D2 (PGD2), which acts as an allergic and inflammatory mediator. The overproduction of PGD2 by H-PGDS causes allergic and inflammatory reactions in the necrotic muscle fibers of Duchenne muscular dystrophy (DMD) patients. Therefore, H-PGDS inhibitors are thought to have potential for use in drug therapy for DMD.The catalytic mechanism of H-PGDS remains unclear, since essential information, such as the binding affinity and stoichiometry of GSH and PGH2 to H-PGDS, have not been precisely determined yet. Therefore, to clarify the issues related to the cofactor and substrate recognition of H-PGDS, we investigated the interaction between H-PGDS and PGH2 in the presence and absence of GSH.For this purpose, isothermal titration calorimetry (ITC) was performed using a substrate mimetics U-44069 in the place of PGH2 since PGH2 is quite unstable in most solutions. Recombinant H-PGDS was prepared using an E. coli expression system and used for the ITC measurements. The results showed that U-44069 binds to H-PGDS in the presence of the cofactor, GSH, but the binding was not significant in the absence of GSH. Therefore, these results suggest that the GSH binding promotes the interaction between H-PGDS and PGH2, and that GSH plays an important role, not only for the catalytic reaction but also for substrate binding.

Effect of age on the occurrence of muscle fiber degeneration associated with myopathies in broiler chickens submitted to feed restriction

To evaluate muscle fiber degeneration (MFD) associated with white striping and wooden breast, pectoralis major of 192 broilers differing for genotype (standard vs. high breast yield), gender, and feeding regime (ad libitum vs. restricted rate 80% from 13 to 21 d of age) were sampled at 14, 21, 28, 35, and 46 d of age for histological analyses by hematoxylin and eosin (H&E) staining to evaluate tissue morphology, Masson's trichrome to identify collagen presence, and Oil red and Nile blue for lipid presence. Microvessels (diameter ≤15 μm), nuclei positive to anti-cleaved lamin A and monoclonal proliferating cell nuclear antigen (PCNA) antisera were counted to assess apoptotic and regenerative processes, respectively. Significant differences were found according to feeding system, age, and their interactions. The frequency of chickens with MFD was higher with ad libitum than restricted feeding (75.0% vs. 62.5%; P = 0.01) and increased with age (18.8%, 28.1%, 75.1%, 96.9%, and 96.9% at 14, 21, 28, 35, and 46 d). However, at 14 d a similar frequency (18.8%) was found in all broilers; at 21 d, MFD occurred more in broilers fed ad libitum than in those under restriction (50.0% vs. 6.3%; P < 0.01); at 28 d differences were reduced (87.5% vs. 62.5%; P = 0.10) to disappear by 35 (100% and 93.8%) and 46 d (96.9% and 96.9%). The number of microvessels decreased with age (20.7 to 9.46; P < 0.001) and the number of nuclei positive to the anti-cleaved lamin A antibody increased. At histology, MFD at 46 d corresponded to loss of typical cross striations, massive necrotic process, degenerating fibers surrounded by inflammatory cells, scattered fibers in an abundant collagen-rich connective tissue, numerous adipose cells; necrotic fibers showed a high percentage of apoptotic nuclei, and regenerating fibers appeared positive to anti-PCNA antibody. In conclusion, MFD soon occurred after 2 wk of growth and increased dramatically within 28 d. Early feed restriction reduced MFD as long as animals were restricted, but no residual effect was recorded after re-alimentation.

Plasma 2-hydroxyglutarate and hexanoylcarnitine levels are potential biomarkers for skeletal muscle toxicity in male Fischer 344 rats.

To identify new candidate biomarkers for skeletal muscle toxicity, an unbiased metabolomic analysis was performed in rats treated with two distinct myotoxicants, cerivastatin (CER) and tetramethyl-p-phenylenediamine (TMPD). Skeletal muscle toxicity was induced in male Fischer 344 rats by administering CER or TMPD and monitored using established endpoints, such as increased plasma creatine kinase (CK) activity and histopathology, and a metabolomic analysis of skeletal muscle and plasma samples. Plasma CK levels in CER-treated rats were markedly elevated at Day 11; however, those in TMPD-treated rats showed a statistically significant decrease at 24 hr after dosing. Light microscopy revealed that vacuolated or necrotic fibers were evident in all CER-treated rats on Day 11, and slightly vacuolated fibers were observed in TMPD-treated rats at 6 and 24 hr after dosing. Metabolomic analysis of the rectus femoris indicated increases in 2-hydroxyglutarate (2HG) in CER-treated rats and hexanoylcarnitine in CER- and TMPD-treated rats. There were also increases in plasma 2HG in CER-treated rats on Days 8 and 11 and in TMPD-treated rats at 24 hr after dosing and increases in plasma hexanoylcarnitine in CER-treated rats on Day 11 and in TMPD-treated rats at 6 and 24 hr after dosing. These experiments demonstrated the potential of plasma 2HG and hexanoylcarnitine as specific and easily detectable biomarkers for skeletal muscle toxicity in rats and demonstrated the value of metabolomics for biomarker detection and identification in toxicological studies.

Effects of Chitosan and Hyaluronic Acid in Healing of Chemically Induced Oral Ulcer in Rabbits

Twelve healthy, local bread male rabbits were used in this study, weighting (1.5-2) kg , divided equally into three groups: in First group (Control group), the ulcers were induced by local application of Sulfuric Acid in concentration 38% in rabbit cheek mucosa ,animals were left without treatment. In second group, same procedure was performed then 0.03 gm of chitosan raw was applied locally on ulcer site twice daily at 1st, 2nd, and 3rd day post induce ulcer while animal under general anesthesia. In third group, same procedure was performed, then saturated gauze with 5 drop of hyfresh drug contain hyalronic acid 2.0 mg\ml were applied locally on ulcer site twice daily at 1st, 2nd, and 3rd day post induces ulcer while animal under general anesthesia.Grossly finding at 3rd day shows limited area of necrotic mucus membrane (m.m) with presence of sluphing area in the second group, while in the control and third groups at same period showed presence of necrotic area of (m.m) surrounded by elevated congestion (m.m), as well as at day 7 evidence regression of necrotic area with definite re-epithelization area in the second group, while in the third group showed advance in regression of necrotic area when compared with earlier period and beginning of re-epithelization, in control group record decreased in necrotized area surrounded by congested area and also small ulcer area was found. Histopathological results in control group at 3rd day showed inflammatory cells particularly neutrophils infiltration between necrotic muscle fibers with hemorrhage in subepithelial layer while in the second group showed granulation tissue consisting from congested blood vessels and marked fibroblast proliferation with collagen fiber deposition, but in the third group showed presence of inflammatory cells particularly neutrophils and macrophages between necrotic muscle fiber. At day 7 in control group showed severe inflammatory cells particularly neutrophils infiltration between marked necrotic muscle fibers, while In the second group at the same period showed thickness collagen fibers with macrophages and lymphocytes infiltration with congested blood vessels, in third group showed inflammatory cells with congested blood vessels, edema, necrotic debris with severe neutrophils infiltration between marked necrotic muscle fiber.

Autoantibodies of Inflammatory Myopathies: Update

Inflammatory myopathies are a heterogeneous group of immune-mediated diseases that involve the skeletal muscle as well as many other organs. In addition to a histological diagnosis at muscle biopsy, the clinical phenotypes of inflammatory myopathies can be defined by the presence of various autoantibodies that are originally detected by RNA or protein immunoprecipitation. However, the correlation between histological features and autoantibodies has not been fully elucidated. Immune-mediated necrotizing myopathy (IMNM), which is characterized by significant necrotic and regeneration muscle fibers with minimal or no inflammatory cell infiltration, is associated with the presence of autoantibodies. IMNM is now classified as a distinct category of inflammatory myopathies, separate from polymyositis, dermatomyositis, and sporadic inclusion body myositis. Here, we divided the autoantibodies of inflammatory myopathies into the following categories: those associated with IMNM, those with activity against aminoacyl transfer RNA synthetase, those associated with dermatomyositis, and those related to other disorders, including overlap syndrome, inclusion body myositis, and primary biliary cirrhosis. The detection of autoantibodies against signal recognition particle or 3-hydroxy-3-methylglutaryl-coenzyme A reductase is useful for the diagnosis of IMNM. The screening of autoantibodies has clinical relevance for managing patients with inflammatory myopathies.

Histopathological changes and biochemical analysis of sulfadiazine injected in egg in chicken embryo pectoral muscles

This study aimed to investigate the effects of different doses of sulfadiazine on embryonic chicken pectoral muscles. In total, 100 fertile eggs were obtained and divided into five groups of control (no injection) and sulfadiazine injection at doses of 2, 10, 30, and 70 mg/kg. After hatching, pectoral muscle tissues were harvested from the newly hatched chickens for histopathological examination and measurement of oxidative stress parameters. Microscopic examination of pectoral muscle samples indicated that sulfadiazine administration changed the histopathological structure of chicken pectoral muscles only at very high doses (30 and 70 mg/kg). Major histopathologic events associated with sulfadiazine cytotoxicity were multifocal degeneration, necrotic tissue changes, and inflammatory cell infiltration (predominantly mononuclear cells) around degenerated and necrotic muscle fibers. Moreover, sulfadiazine at doses of 10, 30 and 70 mg/kg increased malondialdehyde level and decreased glutathione, ferric reducing antioxidant power, and total carotenoid, which indicated oxidative damage in broiler skeletal muscles. Therefore, it could be concluded that in-egg administration of up to 10 mg/kg of sulfadiazine is safe for chicken embryo, whereas dosage of 30 mg/kg (or above) is considered highly toxic.