The impact of dietary phytoestrogens on human health has been a topic of continuous debate since ... more The impact of dietary phytoestrogens on human health has been a topic of continuous debate since their discovery. Nowadays, based on their presumptive beneficial effects, the amount of phytoestrogens consumed in the daily diet has increased considerably worldwide. Thus, there is a growing need for scientific data regarding their mode of action in the human body. Recently, new insights of phytoestrogens’ bioavailability and metabolism have demonstrated an inter-and intra-population heterogeneity of final metabolites’ production. In addition, the phytoestrogens may have the ability to modulate epigenetic mechanisms that control gene expression. This review highlights the complexity and particularity of the metabolism of each class of phytoestrogens, pointing out the diversity of their bioactive gut metabolites. Futhermore, it presents emerging scientific data which suggest that, among well-known genistein and resveratrol, other phytoestrogens and their gut metabolites can act as epige...
ABSTRACT Autopsies represent medical procedures through which the causes of patients’ deaths are ... more ABSTRACT Autopsies represent medical procedures through which the causes of patients’ deaths are determined or, through tissue sampling and microscopic examination of slides in usual stains or special tests, one can offer the basis for understanding the physiopathological mechanisms that contribute to the patients’ death Histological findings of tissue samples from patients who have died of COVID-19 have been mainly orientated to lung, heart, liver, kidney damage with a small percent of them following other organs, but none has, to our knowledge, studied skeletal muscle.
Objectives. Congenital myopathies (CM) are a highly heterogeneous group of disorders with genetic... more Objectives. Congenital myopathies (CM) are a highly heterogeneous group of disorders with genetic cause, characterized by motor deficit and weakness usually manifesting in the neonatal period, with slowly progressive or non-progressive course and affecting both sexes. MC classification has undergone many changes over time, and in recent years molecular genetic studies have enabled identification of novel genes and mutations, thus increasing the diagnostic complexity. We wanted to study the incidence and morphological features of the CM cases diagnosed by muscle biopsy in the Pathology Department of Colentina University Hospital over a period of 10 years (09.2005- 09.2015). Materials and methods. We retrospectively reviewed all the muscle biopsies diagnosed with different types of CM. Muscle biopsies were performed and specifically processed using routine and special stains on cryosections, semithin and ultrathin sections for ultrastructural examination. In all the cases we reassesse...
Objectives. Dysferlinopathies are a group of rare genetic myopathies characterized by muscle weak... more Objectives. Dysferlinopathies are a group of rare genetic myopathies characterized by muscle weakness and atrophy with four distinct clinical phenotypes: Miyoshi myopathy, limb girdle muscular dystrophy type 2B, distal myopathy with anterior tibial onset and an intermediate proximo-distal phenotype. We report a case of dysferlinopathy and discuss relevant clinical, pathological and genetic data. Material and methods. We present the case of a 36 years old man with more than ten years history of progressive muscle weakness and atrophies in the distal lower limbs. He had a first clinical evaluation at the age of 24 years and a muscle biopsy was performed but it was inconclusive. On current admission, he presented with clinical suspicion of Charcot-Marie-Tooth disease, but because of increased serum creatine kinase levels and EMG (electromyography) findings of myopathy, another muscle biopsy was recommended. The muscle tissue obtained was analysed by histopathology, immunohistochemistry...
Skeletal muscle regeneration implies the coordination of myogenesis with the recruitment of myelo... more Skeletal muscle regeneration implies the coordination of myogenesis with the recruitment of myeloid cells and extracellular matrix (ECM) remodelling. Currently, there are no specific biomarkers to diagnose the severity and prognosis of muscle lesions. In order to investigate the gene expression profile of extracellular matrix and adhesion molecules, as premises of homo‐ or heterocellular cooperation and milestones for skeletal muscle regeneration, we performed a gene expression analysis for genes involved in cellular cooperation, migration and ECM remodelling in a mouse model of acute crush injury. The results obtained at two early time‐points post‐injury were compared to a GSE5413 data set from two other trauma models. Third day post‐injury, when inflammatory cells invaded, genes associated with cell‐matrix interactions and migration were up‐regulated. After day 5, as myoblast migration and differentiation started, genes for basement membrane constituents were found down‐regulated,...
Idiopathic inflammatory myopathies (IIM) represent a heterogeneous group of autoimmune diseases w... more Idiopathic inflammatory myopathies (IIM) represent a heterogeneous group of autoimmune diseases whose treatment is often a challenge. Many patients, even after immunosuppressive therapy, do not respond to treatment, so new alternatives have been sought for this. Therefore, other signaling pathways that could contribute to the pathogenesis of myositis have been investigated, such as the expression of myokines in skeletal muscle in response to the inflammatory process. In this review, we will refer to these muscle cytokines that are overexpressed or downregulated in skeletal muscle in patients with various forms of IIM, thus being able to contribute to the maintenance of the autoimmune process. Some muscle cytokines, through their antagonistic action, may be a helpful contributor to the disease modulation, and thus, they could represent personalized treatment targets. Here, we consider the main myokines involved in the pathogenesis of myositis, expressing our view on the possibility o...
Romanian journal of morphology and embryology = Revue roumaine de morphologie et embryologie, 2017
A 25-year-old woman with a five years history of syncope, mild left ventricular hypertrophy and m... more A 25-year-old woman with a five years history of syncope, mild left ventricular hypertrophy and moderately enlarged atria, was diagnosed with third degree atrioventricular heart block alternating with atrioventricular heart block 2:1, and received a dual chamber pacemaker. After three years of evolution, she developed atrial fibrillation, marked biatrial enlargement, severely depressed longitudinal myocardial velocities, associated with mild girdle weakness and slight increase in creatine kinase level. The diagnosis of restrictive cardiomyopathy with mild skeletal myopathy imposed the screening for a common etiology. Skeletal muscle biopsy revealed the morphological picture of myofibrillar myopathy with sarcoplasmic aggregates, immunoreactive for desmin and other ectopic proteins on immunohistochemistry, appearing as granulofilamentous material at ultrastructural level. Western blot analysis confirmed the desmin overexpression. Genetic testing identified a heterozygous missense vari...
Limb-girdle muscular dystrophies (LGMD) are an extremely heterogeneous and rapidly expanding grou... more Limb-girdle muscular dystrophies (LGMD) are an extremely heterogeneous and rapidly expanding group of diseases characterized by progressive weakness of pelvic, scapular and trunk muscles with sparing of facial and distal musculature in most of the subtypes, onset in childhood or in adults of both sexes, very variable clinical severity ranging from mild to severe phenotypes, some associated with cardio-pulmonary and extraskeletal impairment and high serum creatine-kinase (CK) levels. In the past years, huge advances have been recorded in the various identification methods and new distinct entities were discovered. However, it is not yet clear why some muscle groups are affected and others spared in a specific subtype of LGMD, why similar clinical pictures are associated with different genes and mutations, while the same gene or mutation may present with very various clinical phenotypes [1]. In this review we summarize the main aspects of positive and differential diagnosis in LGMD.
Romanian journal of neurology and psychiatry = Revue roumaine de neurologie et psychiatrie
The aim of the present study was to investigate the role of amino acids in the increased seizure ... more The aim of the present study was to investigate the role of amino acids in the increased seizure susceptibility induced by withdrawal of antiepileptic drugs (AEDs). Fifty white Wistar rats treated with AEDs and 30 controls were used. The animals were previously exposed to the acoustic stimulus and only the non responsive were used. The administered AEDs were morphosuximide, ethosuximide, phenobarbital, valproate and gluthetimide. The treatment was discontinued after 2 weeks. The acoustic stimulation was repeated after 2-4 days of abstention. The animals were sacrificed and the amino acids glutamate, aspartate, GABA, glycine and serine were determined in the cortex and the brain stem. The withdrawal of AEDs induced seizure susceptibility in 71% of the rats treated with phenobarbital and in 76% of those receiving morphosuximide. A significant increase of glutamate levels was found in the brain stem following withdrawal of both morphosuximide and ethosuximide. The level of GABA was ele...
Romanian journal of neurology and psychiatry = Revue roumaine de neurologie et psychiatrie
Sixty-four muscle biopsies obtained from patients with Duchenne muscular dystrophy, limb-girdle d... more Sixty-four muscle biopsies obtained from patients with Duchenne muscular dystrophy, limb-girdle dystrophy, congenital muscular dystrophy, or who referred for diagnosis were examined with histochemical methods for dystrophin staining with antidystrophin antibodies. Six atypical cases in whom the dystrophin expression was inconsistent with both clinical and morphopathological pattern were selected: one case of Duchenne muscular dystrophy in whom dystrophin was partially represented, one case referred for investigation in whom dystrophin was absent, despite the lack of clinico-morphological signs supporting the diagnosis of Duchenne disease, two cases of congenital muscular dystrophy in whom dystrophin was absent and one patient with the same diagnosis in whom dystrophin was present, but quantitatively reduced. A patient with limb-girdle muscle dystrophy, in whom immunohistochemical investigation was necessary for the diagnosis is also reported. In conclusion, the immunohistochemical i...
The impact of dietary phytoestrogens on human health has been a topic of continuous debate since ... more The impact of dietary phytoestrogens on human health has been a topic of continuous debate since their discovery. Nowadays, based on their presumptive beneficial effects, the amount of phytoestrogens consumed in the daily diet has increased considerably worldwide. Thus, there is a growing need for scientific data regarding their mode of action in the human body. Recently, new insights of phytoestrogens’ bioavailability and metabolism have demonstrated an inter-and intra-population heterogeneity of final metabolites’ production. In addition, the phytoestrogens may have the ability to modulate epigenetic mechanisms that control gene expression. This review highlights the complexity and particularity of the metabolism of each class of phytoestrogens, pointing out the diversity of their bioactive gut metabolites. Futhermore, it presents emerging scientific data which suggest that, among well-known genistein and resveratrol, other phytoestrogens and their gut metabolites can act as epige...
ABSTRACT Autopsies represent medical procedures through which the causes of patients’ deaths are ... more ABSTRACT Autopsies represent medical procedures through which the causes of patients’ deaths are determined or, through tissue sampling and microscopic examination of slides in usual stains or special tests, one can offer the basis for understanding the physiopathological mechanisms that contribute to the patients’ death Histological findings of tissue samples from patients who have died of COVID-19 have been mainly orientated to lung, heart, liver, kidney damage with a small percent of them following other organs, but none has, to our knowledge, studied skeletal muscle.
Objectives. Congenital myopathies (CM) are a highly heterogeneous group of disorders with genetic... more Objectives. Congenital myopathies (CM) are a highly heterogeneous group of disorders with genetic cause, characterized by motor deficit and weakness usually manifesting in the neonatal period, with slowly progressive or non-progressive course and affecting both sexes. MC classification has undergone many changes over time, and in recent years molecular genetic studies have enabled identification of novel genes and mutations, thus increasing the diagnostic complexity. We wanted to study the incidence and morphological features of the CM cases diagnosed by muscle biopsy in the Pathology Department of Colentina University Hospital over a period of 10 years (09.2005- 09.2015). Materials and methods. We retrospectively reviewed all the muscle biopsies diagnosed with different types of CM. Muscle biopsies were performed and specifically processed using routine and special stains on cryosections, semithin and ultrathin sections for ultrastructural examination. In all the cases we reassesse...
Objectives. Dysferlinopathies are a group of rare genetic myopathies characterized by muscle weak... more Objectives. Dysferlinopathies are a group of rare genetic myopathies characterized by muscle weakness and atrophy with four distinct clinical phenotypes: Miyoshi myopathy, limb girdle muscular dystrophy type 2B, distal myopathy with anterior tibial onset and an intermediate proximo-distal phenotype. We report a case of dysferlinopathy and discuss relevant clinical, pathological and genetic data. Material and methods. We present the case of a 36 years old man with more than ten years history of progressive muscle weakness and atrophies in the distal lower limbs. He had a first clinical evaluation at the age of 24 years and a muscle biopsy was performed but it was inconclusive. On current admission, he presented with clinical suspicion of Charcot-Marie-Tooth disease, but because of increased serum creatine kinase levels and EMG (electromyography) findings of myopathy, another muscle biopsy was recommended. The muscle tissue obtained was analysed by histopathology, immunohistochemistry...
Skeletal muscle regeneration implies the coordination of myogenesis with the recruitment of myelo... more Skeletal muscle regeneration implies the coordination of myogenesis with the recruitment of myeloid cells and extracellular matrix (ECM) remodelling. Currently, there are no specific biomarkers to diagnose the severity and prognosis of muscle lesions. In order to investigate the gene expression profile of extracellular matrix and adhesion molecules, as premises of homo‐ or heterocellular cooperation and milestones for skeletal muscle regeneration, we performed a gene expression analysis for genes involved in cellular cooperation, migration and ECM remodelling in a mouse model of acute crush injury. The results obtained at two early time‐points post‐injury were compared to a GSE5413 data set from two other trauma models. Third day post‐injury, when inflammatory cells invaded, genes associated with cell‐matrix interactions and migration were up‐regulated. After day 5, as myoblast migration and differentiation started, genes for basement membrane constituents were found down‐regulated,...
Idiopathic inflammatory myopathies (IIM) represent a heterogeneous group of autoimmune diseases w... more Idiopathic inflammatory myopathies (IIM) represent a heterogeneous group of autoimmune diseases whose treatment is often a challenge. Many patients, even after immunosuppressive therapy, do not respond to treatment, so new alternatives have been sought for this. Therefore, other signaling pathways that could contribute to the pathogenesis of myositis have been investigated, such as the expression of myokines in skeletal muscle in response to the inflammatory process. In this review, we will refer to these muscle cytokines that are overexpressed or downregulated in skeletal muscle in patients with various forms of IIM, thus being able to contribute to the maintenance of the autoimmune process. Some muscle cytokines, through their antagonistic action, may be a helpful contributor to the disease modulation, and thus, they could represent personalized treatment targets. Here, we consider the main myokines involved in the pathogenesis of myositis, expressing our view on the possibility o...
Romanian journal of morphology and embryology = Revue roumaine de morphologie et embryologie, 2017
A 25-year-old woman with a five years history of syncope, mild left ventricular hypertrophy and m... more A 25-year-old woman with a five years history of syncope, mild left ventricular hypertrophy and moderately enlarged atria, was diagnosed with third degree atrioventricular heart block alternating with atrioventricular heart block 2:1, and received a dual chamber pacemaker. After three years of evolution, she developed atrial fibrillation, marked biatrial enlargement, severely depressed longitudinal myocardial velocities, associated with mild girdle weakness and slight increase in creatine kinase level. The diagnosis of restrictive cardiomyopathy with mild skeletal myopathy imposed the screening for a common etiology. Skeletal muscle biopsy revealed the morphological picture of myofibrillar myopathy with sarcoplasmic aggregates, immunoreactive for desmin and other ectopic proteins on immunohistochemistry, appearing as granulofilamentous material at ultrastructural level. Western blot analysis confirmed the desmin overexpression. Genetic testing identified a heterozygous missense vari...
Limb-girdle muscular dystrophies (LGMD) are an extremely heterogeneous and rapidly expanding grou... more Limb-girdle muscular dystrophies (LGMD) are an extremely heterogeneous and rapidly expanding group of diseases characterized by progressive weakness of pelvic, scapular and trunk muscles with sparing of facial and distal musculature in most of the subtypes, onset in childhood or in adults of both sexes, very variable clinical severity ranging from mild to severe phenotypes, some associated with cardio-pulmonary and extraskeletal impairment and high serum creatine-kinase (CK) levels. In the past years, huge advances have been recorded in the various identification methods and new distinct entities were discovered. However, it is not yet clear why some muscle groups are affected and others spared in a specific subtype of LGMD, why similar clinical pictures are associated with different genes and mutations, while the same gene or mutation may present with very various clinical phenotypes [1]. In this review we summarize the main aspects of positive and differential diagnosis in LGMD.
Romanian journal of neurology and psychiatry = Revue roumaine de neurologie et psychiatrie
The aim of the present study was to investigate the role of amino acids in the increased seizure ... more The aim of the present study was to investigate the role of amino acids in the increased seizure susceptibility induced by withdrawal of antiepileptic drugs (AEDs). Fifty white Wistar rats treated with AEDs and 30 controls were used. The animals were previously exposed to the acoustic stimulus and only the non responsive were used. The administered AEDs were morphosuximide, ethosuximide, phenobarbital, valproate and gluthetimide. The treatment was discontinued after 2 weeks. The acoustic stimulation was repeated after 2-4 days of abstention. The animals were sacrificed and the amino acids glutamate, aspartate, GABA, glycine and serine were determined in the cortex and the brain stem. The withdrawal of AEDs induced seizure susceptibility in 71% of the rats treated with phenobarbital and in 76% of those receiving morphosuximide. A significant increase of glutamate levels was found in the brain stem following withdrawal of both morphosuximide and ethosuximide. The level of GABA was ele...
Romanian journal of neurology and psychiatry = Revue roumaine de neurologie et psychiatrie
Sixty-four muscle biopsies obtained from patients with Duchenne muscular dystrophy, limb-girdle d... more Sixty-four muscle biopsies obtained from patients with Duchenne muscular dystrophy, limb-girdle dystrophy, congenital muscular dystrophy, or who referred for diagnosis were examined with histochemical methods for dystrophin staining with antidystrophin antibodies. Six atypical cases in whom the dystrophin expression was inconsistent with both clinical and morphopathological pattern were selected: one case of Duchenne muscular dystrophy in whom dystrophin was partially represented, one case referred for investigation in whom dystrophin was absent, despite the lack of clinico-morphological signs supporting the diagnosis of Duchenne disease, two cases of congenital muscular dystrophy in whom dystrophin was absent and one patient with the same diagnosis in whom dystrophin was present, but quantitatively reduced. A patient with limb-girdle muscle dystrophy, in whom immunohistochemical investigation was necessary for the diagnosis is also reported. In conclusion, the immunohistochemical i...
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