RESUMO
Nephron number at birth has relevant clinical importance with implications for long-term renal health. In recent years, the podocyte depletion hypothesis has emerged as an important concept in kidney pathology. This study was aimed at verifying whether human podocyte number changes significantly during intrauterine life. To this end, 62 subjects with gestational ages ranging from 20 to 41 wk were examined. Kidney sections were stained with hematoxylin and eosin and digitally scanned at ×400 magnification. Subjects were subdivided into fetuses (gestational age≤24 wk, n=5), preterms (gestational age≥25 and ≤36 wk, n=39), and full-term newborns (gestational age≥37 wk, n=18). The average podocyte number of 1,908±645, 1,394±498, and 1,126±256 was, respectively, observed in fetuses, preterms, and full-term newborns. A significant main effect (P=0.0051) of gestational age on podocyte number was observed with a significantly lower number in full-term newborns than in fetuses (P<0.01). Intragroup variability was also observed. We speculate that variations in podocyte number could be correlated with factors such as drugs and maternal diet occurring during intrauterine life. In conclusion, this study shows, for the first time, a decreasing trend in podocyte number during gestation.
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Rim/embriologia , Podócitos/patologia , Autopsia , Feminino , Idade Gestacional , Humanos , Recém-Nascido , MasculinoRESUMO
The cytochrome P450 superfamily (CYP450) in humans is formed by 57 functional monooxygenases critical for the metabolism of numerous endogenous and exogenous compounds. The superfamily is organized into 18 families and 44 subfamilies. CYP nomenclature is based on the identity of amino acids. The most important functions of the CYP450 are related to metabolism of endogenous compounds, detoxification of exogenous xenobiotics and decomposition of the vast majority of currently used drugs. The expression of CYP450 enzymes in the human body is characterized by a marked substrate and tissue specificity, the most important being localized in the liver, but also present in kidney, lung, brain, breast, prostate and in the small intestine. The human cytochrome P450 3A gene family (CYP3A) accounts for the largest portion of CYP450 proteins in human liver and includes 4 genes: CYP3A4, CYP3A5, CYP3A7, CYP3A43. Multiple and complex genetic variations, marked interindividual, interethnic and gender variability have been reported regarding CYP3A isoform expression and activity. Multiple factors may affect CYP3A expression and activity, such as inducers like rifampicin, phenobarbital, 3-methylcholantrene, beta-naphtoflavone, and dexamethasone. The maturation of organ systems, paralleled by ontogeny of drug-metabolizing enzymes during fetal life and in the first months of postnatal life, surely exerts profound effects on drug disposition, probably being the predominant factor accounting for age-associated changes in drug clearance. In fact, drug dosage in the perinatal period represents a continuous challenge for neonatologists. The purpose of this article is to provide a brief review of the pharmacokinetic differences between neonates and adults, showing the peculiarities of liver CYP450-related drug metabolism in the perinatal period and at birth, and to report the toxic mechanisms of liver injury in neonates, due to the most frequently utilized drugs in NICU centers.
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Sistema Enzimático do Citocromo P-450/genética , Neonatologia , Preparações Farmacêuticas/metabolismo , Polimorfismo Genético , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/genética , Humanos , Recém-Nascido , Fígado/efeitos dos fármacos , Fígado/enzimologia , Fígado/patologia , Medicina de PrecisãoRESUMO
BACKGROUND: An increasing number of coronavirus disease 2019 (COVID-19) related autoimmune hepatitis (AIH) and autoimmune liver disease (AILD) has been already described so far in the last three years. This rise has set up some diagnostic and therapeutic concerns, although steroid therapy has mostly been efficient, avoiding main significant side effects. CASE REPORT: We report the case of a 52-year-old subject displaying liver function impairment at the laboratory tests while positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) swab. Needle liver biopsy showed severe portal inflammation, interface hepatitis, lobular inflammation, abundant plasma cells, bridging necrosis, endothelialitis, bile duct vanishing disease, and ductular reaction. The diagnosis of autoimmune liver disease (AILD) was performed. After a month of steroid and ursodeoxycholic acid medications, liver function fully recovered. Azathioprine was introduced, and steroids were gradually reduced. CONCLUSIONS: Probably triggered by the SARS-CoV-2-induced cytokine storm, the association between COVID-19 and autoimmune-related inflammatory injury may display a particular paradigm of AILD pathogenesis.
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Doenças dos Ductos Biliares , COVID-19 , Hepatite Autoimune , Hepatopatias , Humanos , Pessoa de Meia-Idade , SARS-CoV-2 , COVID-19/complicações , Hepatopatias/diagnóstico , Hepatopatias/tratamento farmacológico , Hepatopatias/etiologia , Hepatite Autoimune/diagnóstico , Hepatite Autoimune/tratamento farmacológico , Inflamação , Ácido Ursodesoxicólico/uso terapêuticoRESUMO
In this narrative review we report the main relationships between trace metals and the hemostatic system since this aspect has seldom attracted the attention of the scientific community. A basic aspect to be considered is the importance of maintaining the fine control of all trace metals' levels since they have an important impact on the pathophysiology of the hemostatic system. It is worth noting that poor diet habits are responsible for most trace metal deficiencies, while pollution is responsible for dangerous exposure to them with a consequent negative impact on the general population. This appears of paramount importance in planning the implementation of food and nutrient support to ameliorate the hidden hunger and the quality of life of people especially in developing countries and limiting poisons both in the air and food. As it often happens, when damage to certain mechanisms takes a very long time to appear, no attention is paid to the importance of a systematic prevention to avoid late negative outcomes.
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Hemostáticos , Oligoelementos , Humanos , Zinco , Qualidade de Vida , CádmioRESUMO
OBJECTIVE: ISL1 is a pioneer transcription factor that plays important roles in cell lineage specification and differentiation, by programming the epigenome and recruiting additional regulatory factors. The aim of this study is to determine whether the human breastmilk contains ISL1-positive stem cells, and, if so, to describe the subcellular localization of ISL1. MATERIALS AND METHODS: Breast milk was obtained from fourteen healthy females during the first 2-6 months of lactation. Cell morphology was examined in the breast milk with the automatic ThinPrep® processor (Hologic® Inc.) in commercial Cytological ThinPrep® solution (Hologic® Inc.), followed by standard immunohistochemical staining of ISL1. RESULTS: ISL1 had a granular diffuse cytoplasmic localization, with varying intensity of staining in both single and grouped cells. Nuclear staining was also present, as was staining of intracellular and extracellular vesicles with ISL1 antibody. CONCLUSIONS: These preliminary results suggest that ISL1 could distinguish a readily available source of putative stem cells in human breast milk. These stem cells may complete the network created between the mother and the newborn during gestation, thereby improving the efficiency of programming and reprogramming postnatal events.
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Leite Humano , Fatores de Transcrição , Feminino , Humanos , Recém-Nascido , Diferenciação Celular , Regulação da Expressão Gênica , Miócitos Cardíacos/metabolismo , Fatores de Transcrição/genéticaRESUMO
OBJECTIVE: The notochord acts as a patterning structure, playing a key role in the formation of the vertebral column, both indirectly by inducing sclerotome cell differentiation and directly by forming the nucleus pulposus of intervertebral discs. The abnormal development of the notochord results in an easy equation with a variety of birth defects. Therefore, we focused our attention on the analysis of the early stages of human notochord development by highlighting the role of progenitor stem cells involved in the origin of intervertebral discs (IVDs). MATERIALS AND METHODS: Eight human fetuses, ranging from 8 up to 21 weeks of gestational age, were obtained from spontaneous abortion or voluntary interruption of gestation. Samples were 10% formalin-fixed, routinely processed, and paraffin-embedded. Five micron-tick paraffin sections were obtained from each sample. Sections were stained with hematoxylin-eosin and PAS stain for a morphological examination. Tissue samples were immunostained with a commercial anti-human CD44 rabbit monoclonal antibody at 1:100 dilution. RESULTS: Immunoreactivity for CD44 was detected in six out of eight notochords examined in this study. Reactivity for CD44 was restricted to progenitor cells giving rise to the nucleus pulposus (NP) of the developing IVDs. Positive cells showed a membranous and/or cytoplasmic immunostaining, no reactivity was observed in the nuclear compartment. CD44 expression was always restricted to IVD precursor cells, whereas cartilage precursors were devoid of labelling. CONCLUSIONS: Our study shows, for the first time, that the stem cell marker CD44 selectively marks intervertebral disc progenitor cells, paralleling their differentiation toward a discogenic phenotype. Therefore, our results suggest that CD44 plays a key role in IVD development, allowing its differentiation from surrounding undifferentiated notochordal cells toward a IVD phenotype. Given the role of CD44 in IVD development, we may hypothesize that low CD44 levels might be associated with changes in IVD development and with susceptibility to develop back pain later in life.
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Notocorda , Núcleo Pulposo , Feminino , Gravidez , Humanos , Células-Tronco , Diferenciação Celular , Coluna Vertebral , Receptores de HialuronatosRESUMO
OBJECTIVE: Acyl-CoA-binding protein (ACBP), also known as diazepam binding inhibitor (DBI), is a small phylogenetically conserved protein. This ancestral peptide is multifunctional, performing intracellular activities as ACBP protein or extracellular roles as DBI. Several studies showed its endless facets, including a relevant activity as appetite stimulator and as anabolic factor. High levels of ACBP have been described in erythrocytes, liver, kidney, and gut cells. The aim of this study was to analyze, at immunohistochemical level, the expression of ACBP in fetal human tissues during development, focusing on the developing kidney. MATERIALS AND METHODS: Immunohistochemistry for ACBP was performed on 30 human fetal kidneys, from 15 fetuses of gestational age ranging from 13 to 19 weeks. At autopsy, all kidney samples were 10% formalin-fixed, routinely processed and paraffin-embedded. Five micron-thick paraffin sections were stained with Hematoxylin and Eosin and PAS stain for a morphological examination. RESULTS: ACBP was detected in all 30 kidneys analyzed in this study. No significant changes in ACBP expression were observed at different gestational ages. Immunostaining for ACBP was restricted to the epithelium covering the renal pelvis, the papillae, the collecting tubules, and the proximal and distal tubules. On the other hand, medullary regions and in the metanephric mesenchymal stem/progenitor cells did not show any reactivity for ACBP. CONCLUSIONS: According to our findings, ACBP should be considered as a new player in the complex field of human nephrogenesis, given that it was detected in all fetal kidneys immunostained. Its preferential localization in the renal structures derived from the Wolf duct, such as pelvis epithelium and collecting ducts, suggests a major role for ACBP in the induction of the metanephric mesenchymal cells toward the differentiation into glomerular structures. ACBP expression in proximal and distal tubules, two structures originating from the metanephric mesenchyme, indicates a further role of this protein in nephron development. In conclusion, ACBP should be added to the multiple molecules involved in human nephrogenesis.
Assuntos
Inibidor da Ligação a Diazepam , Rim , Coenzima A/metabolismo , Humanos , Rim/embriologia , Rim/metabolismoRESUMO
OBJECTIVE: L1 cell adhesion molecule (L1CAM) is a member of the immunoglobulin superfamily of cell adhesion molecules. The present study investigated the expression of L1CAM during the development in the fetal human kidney at different gestational ages, to reach a better knowledge on the role of L1CAM in renal morphogenesis. MATERIALS AND METHODS: The immunohistochemical analysis for L1CAM was performed in 24 fetal kidneys of different gestational ages, ranging from 10 to 38 weeks. L1CAM expression was observed in all 24 kidneys examined. RESULTS: Immunoreactivity for L1CAM was restricted to the collecting tubules, of the developing fetal kidneys. Moreover, L1CAM was detected in the ureteric bud tips, near the subcapsular metanephric mesenchymal stem/progenitor cells. L1CAM was also expressed in the collecting tubules undergoing fusion with the distal tubules of the developing nephrons. L1CAM was mainly expressed along the cell membrane. In fetal kidneys in which the renal pelvis was observed, epithelial cells of the renal pelvis showed strong membranous reactivity for L1CAM. CONCLUSIONS: Our study shows that L1CAM is expressed in all stages of human kidney nephrogenesis, being restricted to the renal structures derived from the ureteric bud. The expression of L1CAM in the cells of the ureteric bud tips suggests a major role for this adhesion molecule in the induction of metanephric mesenchymal cells to undergo mesenchymal-to-epithelial transition and differentiation into new nephrons. The interindividual variability in L1CAM expression observed in this study might be related to different levels of nephrogenesis, suggesting L1CAM involvement in the fetal programming of adult kidney diseases.
Assuntos
Nefropatias/genética , Rim/crescimento & desenvolvimento , Molécula L1 de Adesão de Célula Nervosa/genética , Adulto , Idade Gestacional , Humanos , Lactente , Rim/metabolismo , NéfronsRESUMO
OBJECTIVE: Previous studies have confirmed the key mechanism by which SARS-CoV-2 enters human cells. It is well established that ACE2 is the receptor that can mark the beginning of the infection. In light of this, the organs that express higher levels of ACE2 are generally considered at higher risk, while those with lower levels should be somehow more protected. This - if related to the scarcity of ace2-expressing cells in the brain - seems to contrast with the presence of a variety of neurological symptoms that follow infection with ace2. The aim of this work was to analyze ACE2 expression in the human brain, focusing on the choroid plexuses. PATIENTS AND METHODS: Twenty brain samples were obtained at autopsy from ten human fetuses and from ten adult subjects. All samples were selected to contain the choroid plexus. Specimens were fixed in 10% formalin, routinely processed and paraffin embedded. 5-micron sections were stained with Hematoxylin and Eosin (H&E) and immunostained with a commercial anti-human ACE2 rabbit monoclonal antibody at 1:100 dilution. RESULTS: We analyzed 20 samples by immunohistochemistry, and we noted that, as far as fetal samples are concerned, a strong reactivity for ACE2 was detected in the myxoid stroma of the choroid plexuses and in the endothelial cells in fetuses. The complete absence of the ACE2 marker was detected in epithelial cells, neurons and glial cells of the cerebral cortex, both in fetuses and in adults. Whereas a strong but selective reactivity for ACE2 was also detected in adult choroid plexuses, mainly localized in the endothelial cells of the choroid capillaries. CONCLUSIONS: Our study shows a strong expression of ACE in the fetal and adult brain choroid plexuses. This new histopathological finding may clarify the susceptibility of the human brain to SARS-COV-2 infection. Our data indicate the choroid plexus as the entry gate of virus for in the human brain; therefore, the entrance of SARS-CoV-2 into the cerebrospinal fluid through the choroid plexuses might represent the mechanism utilized by this coronavirus to cause direct injury to brain cells.
Assuntos
Enzima de Conversão de Angiotensina 2 , COVID-19 , Corioide , Plexo Corióideo , Células Endoteliais , Humanos , SARS-CoV-2RESUMO
OBJECTIVE: L1 cell adhesion molecule (L1CAM) is a glycoprotein characterized by three components: an extracellular region, a transmembrane segment, and a cytoplasmic tail. L1CAM is expressed in multiple human cells, including neurons. The neural cell adhesion molecule L1 has been implicated in a variety of neurologic processes, including neuritogenesis and cerebellar cell migration. The presence of L1CAM on the surface of nerve cells allows the adhesion of neurons among them. Furthermore, when it is bound to itself or to other proteins, L1-CAM induces signals inside the cell. The aim of this work was to study L1CAM expression in the human spinal cord during development, at different gestational ages, through immunohistochemistry. MATERIALS AND METHODS: Immunohistochemical analysis for L1CAM was performed in five human spinal cord samples, including three embryos and two fetuses of different gestational ages, ranging from 8 to 12 weeks. RESULTS: L1CAM expression was detected in all 5 spinal cords examined in this study. The adhesion molecule was found in the vast majority of cells. The highest levels of immunoreactivity for L1CAM were detected at the periphery of the developing organs, in the spinal cord zones occupied by sensory and motor fibers. In the alar and basal columns, immunoreactivity for L1CAM was characterized by a reticular pattern, being mainly expressed in axons. Strong reactivity of L1CAM was also found in extracellular vesicles. This extracellular localization might indicate the ability of L1CAM to mediate the transduction of extracellular signals that support axon outgrowth. CONCLUSIONS: The high reactivity of L1cam in the axons of developing neurons in the fetal spinal cord confirms previous studies on the ability of L1CAM to promote axon sprouting and branching in the developing nervous system. In this work, a new actor is reported to have a role in the complex field of human spinal cord development: L1CAM, whose expression is highly found in the developing neuronal and glial precursors.
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Vesículas Extracelulares , Molécula L1 de Adesão de Célula Nervosa , Medula Espinal , Axônios/metabolismo , Embrião de Mamíferos , Vesículas Extracelulares/metabolismo , Humanos , Lactente , Molécula L1 de Adesão de Célula Nervosa/genética , Molécula L1 de Adesão de Célula Nervosa/metabolismo , Medula Espinal/embriologia , Medula Espinal/crescimento & desenvolvimento , Medula Espinal/metabolismoRESUMO
Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare new syndrome occurring after the ChAdOx1 nCoV-19 vaccine immunization. Patients with VITT are characterized by a variable clinical presentation, likewise also the outcome of these patients is very variable. Here we report the lung ultrastructural findings in the course of VITT of a 58-year-old male patient. Alveoli were mainly dilated, irregular in shape, and occupied by a reticular network of fibrin, while interalveolar septa appeared thickened. The proliferation of small capillaries gave rise to plexiform structures and pulmonary capillary hemangiomatosis-like features. Near the alveoli occupied by a dense fibrin network, the medium-sized arteries showed a modified wall and an intraluminal thrombus. This scenario looks quite similar to that found during COVID-19, where the lungs suffer from the attack of the antigen-antibodies complexes and the virus respectively. In both diseases, the final outcome is a severe inflammation, activation of the haemostatic system and fibrinolysis.
Assuntos
ChAdOx1 nCoV-19/efeitos adversos , Lesão Pulmonar/etiologia , Lesão Pulmonar/patologia , Púrpura Trombocitopênica Idiopática/induzido quimicamente , Vacinação/efeitos adversos , COVID-19/prevenção & controle , ChAdOx1 nCoV-19/imunologia , Fibrina , Humanos , Lesão Pulmonar/diagnóstico por imagem , Lesão Pulmonar/imunologia , Masculino , Microscopia Eletrônica de Varredura , Pessoa de Meia-Idade , Tecido Parenquimatoso/patologia , Púrpura Trombocitopênica Idiopática/diagnóstico , Púrpura Trombocitopênica Idiopática/imunologiaRESUMO
The growing incidence of cancers is pushing oncologists to find out new explanations other than the somatic mutation theory, based on the accumulation of DNA mutations. In particular, the embryo-fetal exposure to an increasing number of environmental factors during gestation might represent a trigger able to influence the susceptibility of the newborn to develop cancer later in life. This idea agrees with the fetal programming theory, also known as the Barker hypothesis. Here the role of insulin-like growth factors, thymosin beta-4, and epigenome are discussed as mediators of cancer in prenatal human development. The role of epigenetic factors that during gestation increase the predisposition to develop cancer and the similarities in the gene expression (like MMP9, OPN, TP53 and CDKN2A) between embryonic development and cancer are key factors. Likewise, maternal obesity might be able to re-program embryo-fetal development with long-term changes, including an increased risk to develop neuroblastoma and acute leukemia. Birth weight alone and birth weight corrected for gestational age are proposed as important variables capable of predicting the vulnerability to develop cancers. According to the findings here reported, we hypothesize that cancer prevention should start during gestation by improving the quality of maternal diet. In conclusion, the Barker hypothesis should be applied to cancer as well. Therefore, the identification of the epigenetic factors of cancer appears mandatory, so that the cancer prevention might start in the womb before birth.
Assuntos
Desenvolvimento Fetal , Neoplasias , Peso ao Nascer , Carcinogênese , Epigenômica , Feminino , Desenvolvimento Fetal/genética , Humanos , Recém-Nascido , Neoplasias/genética , GravidezRESUMO
OBJECTIVE: Patients with 2019-nCoV infection have a high risk to develop venous thrombotic events. Several guidelines recommend the use of either unfractionated heparin or low molecular weight heparins in preventing thrombotic events in these patients. However, results from clinical studies, so far published, reached controversial conclusions on heparin efficacy in this kind of patients since the incidence of venous thromboembolism remains high despite prophylaxis. This narrative review aims to provide an overview of the antiviral and anti-inflammatory properties of heparins and their efficacy and safety in SARS-CoV-2 medical ward-patients. Moreover, anatomical findings and ongoing trials are also reported. Finally, this narrative review tries to explain why heparins fail to prevent venous thrombosis. MATERIALS AND METHODS: We searched for the most relevant published studies on heparins and 2019-nCoV infected patients using the MEDLINE electronic database in the period between January and December 2020. Articles were preliminarily defined as eligible if they: a) were in English language, b) enrolled 250 or more medical ward-patients and 100 or more ICU-patients, c) reported results on patients treated with heparins in a percentage of at least 70% and d) performed an objectively confirmed diagnosis of VTE. RESULTS: Data from medium to large scientific studies show that the incidence of venous thrombotic events in medical ward-patients with SARS-CoV-2 vary between 0% and 8.3%, while this rate is higher, from 6.2% to 49%, in Intensive Care Unit-patients. However, heparins reduce the mortality rate in these patients of about 50%. Histological findings show that thrombosis could affect capillaries, main and small-mid-sized vessels, and it is associated with diffuse alveolar damage. CONCLUSIONS: Heparins have anti-inflammatory and anti-viral properties, which may be of help in reducing mortality in SARS-CoV-2 patients. Failure of heparins at prophylactic dosages in preventing VTE, especially in ICU-patients, could be due to the severity of the disease. Data on the use of heparins in an early phase of the 2019-nCoV infection are still lacking.
Assuntos
Anticoagulantes/uso terapêutico , Tratamento Farmacológico da COVID-19 , Heparina/uso terapêutico , Tromboembolia Venosa/tratamento farmacológico , Animais , Anti-Inflamatórios/uso terapêutico , Antivirais/uso terapêutico , COVID-19/epidemiologia , COVID-19/imunologia , Humanos , Mortalidade/tendências , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Tromboembolia Venosa/epidemiologia , Tromboembolia Venosa/imunologiaRESUMO
Microanatomy of the vast majority of human organs at birth is characterized by marked differences as compared to adult organs, regarding their architecture and the cell types detectable at histology. In preterm neonates, these differences are even more evident, due to the lower level of organ maturation and to ongoing cell differentiation. One of the most remarkable finding in preterm tissues is the presence of huge amounts of stem/progenitor cells in multiple organs, including kidney, brain, heart, adrenals, and lungs. In other organs, such as liver, the completely different burden of cell types in preterm infants is mainly related to the different function of the liver during gestation, mainly focused on hematopoiesis, a function that is taken by bone marrow after birth. Our preliminary studies showed that the antigens expressed by stem/progenitors differ significantly from one organ to the next. Moreover, within each developing human tissue, reactivity for different stem cell markers also changes during gestation, according with the multiple differentiation steps encountered by each progenitor during development. A better knowledge of stem/progenitor cells of preterms will allow neonatologists to boost preterm organ maturation, favoring the differentiation of the multiple cells types that characterize each organ in at term neonates.
RESUMO
OBJECTIVE: Atherosclerosis is one of the leading causes of disability and mortality worldwide. Inflammation, including monocytes, T and B cells, plays a key role in its pathogenesis. Our purpose was to evaluate plasma cells' presence in a large series of carotid artery plaques and the clinical association. PATIENTS AND METHODS: Forty-eight consecutive patients treated with carotid endarterectomy were retrospectively analyzed to assess plasma cells' presence inside the plaque. A semiquantitative grading score was applied, ranging from absence, scattered, clusters of 5-10, and sheets of >10 plasma cells. Plasma cell's location, as intraplaque, subendothelial or peri-adventitial, was also defined. RESULTS: In 75% of plaques analyzed, plasma cells were detected: scattered in 63.9%, in clusters in 22.2%, and in sheets in 13.9% of cases. In all cases, plasma cells were observed only inside the plaque. In 13.9% and in 11.1% of cases, plasma cells showed, respectively, a concomitant subendothelial or peri-adventitial distribution. In 5.6% of plaques, there was a simultaneous distribution in subendothelial, peri-adventitial layer, and intraplaque. Association between the presence of symptoms and plasma cells infiltrate was found. CONCLUSIONS: Our results suggest that plasma cells could be a key parameter linked to plaque instability. Some types of configurations are significantly associated with the occurrence of cerebrovascular symptoms.
Assuntos
Estenose das Carótidas/imunologia , Plasmócitos/imunologia , Idoso , Idoso de 80 Anos ou mais , Estenose das Carótidas/cirurgia , Endarterectomia das Carótidas , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: Platelets, blood coagulation along with fibrinolysis are greatly involved in the pathophysiology of infectious diseases induced by bacteria, parasites and virus. This phenomenon is not surprising since both the innate immunity and the hemostatic systems are two ancestral mechanisms which closely cooperate favoring host's defense against foreign invaders. However, the excessive response of these systems may be dangerous for the host itself. MATERIALS AND METHODS: We searched and retrieved the articles, using the following electronic database: MedLine and Embase. We limited our search to articles published in English, but no restrictions in terms of article type, publication year, and geography were adopted. RESULTS: The hemostatic phenotype of the infectious diseases is variable depending on the points of attack of the different involved pathogens. Infectious diseases which show a prothrombotic phenotype are bacterial sepsis, SARS-CoV-2 and malaria. However, among the bacterial sepsis, Yersinia Pestis is characterized by a profibrinolytic behavior. On the contrary, the hemorrhagic fevers, due to Dengue and Ebola virus, mainly exploit the activation of fibrinolysis secondary to a huge endothelial damage which can release a large amount of t-PA in the early phase of the diseases. CONCLUSIONS: Blood coagulation and fibrinolysis are greatly activated based on the strategy of the different infectious agents which exploit the excess of response of both systems to achieve the greatest possible virulence.
Assuntos
Coagulação Sanguínea , COVID-19/patologia , Fibrinólise , COVID-19/complicações , COVID-19/virologia , Células Endoteliais/citologia , Células Endoteliais/metabolismo , Células Endoteliais/virologia , Eritrócitos/citologia , Eritrócitos/metabolismo , Eritrócitos/parasitologia , Humanos , Monócitos/citologia , Monócitos/metabolismo , Monócitos/virologia , SARS-CoV-2/isolamento & purificação , Tromboplastina/metabolismo , Vírus/patogenicidadeRESUMO
OBJECTIVE: In liver cirrhosis, a complex coagulopathy does exist. The aim was to investigate whether a possible chronic consumption coagulopathy is the underlying phenomenon of the disease. PATIENTS AND METHODS: We measured endogenous thrombin generation with and without thrombomodulin (ETP ratio) along with D-Dimer in a group of consecutive 282 cirrhotic patients. Fibrinogen, Platelet count and the Hemorrhagic score were previously computed in the same patients. The ETP ratio represents the resistance to the anticoagulant activity of TM and should be considered as an index of a procoagulant imbalance. RESULTS: ETP ratio and D-Dimer showed higher values in the cirrhotic patients when compared to controls thus showing a hypercoagulable state. When the patients were divided based on the Hemorrhagic score >7, we found that Fibrinogen, ETP ratio, D-Dimer and the platelet count were significantly different between the two groups. Again, when we considered ETP ratio >0.88, the median value of the cirrhotic patients, all parameters, were statistically different between the two groups. D-Dimer were higher while fibrinogen and platelet count were statistically lower in cirrhotic patients with higher ETP ratio values. Even when the same patients were divided based on their platelet count (> 100 x 109/L) the results showed a similar behavior. ROC curves showed significant AUCs when the hemorrhagic score was challenged against Fibrinogen, D-Dimer, Platelet count and ETP ratio. CONCLUSIONS: In liver cirrhosis hypercoagulable state is associated with an increase in D-Dimer levels along with a decrease in fibrinogen and platelet count thus indicating a low-grade intravascular coagulation which predicts a high hemorrhagic risk.
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Transtornos da Coagulação Sanguínea/fisiopatologia , Coagulação Intravascular Disseminada/fisiopatologia , Hemorragia/epidemiologia , Cirrose Hepática/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Hemorragia/etiologia , Humanos , Cirrose Hepática/sangue , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Estudos Retrospectivos , Risco , Trombina/metabolismo , Trombomodulina/metabolismoRESUMO
OBJECTIVE: Acute respiratory distress syndrome (ARDS) is characterized by quantitative and qualitative changes in surfactant composition, leading to surfactant dysregulation with alveolar collapse and acute respiratory hypoxic failure. Recently, surfactant has been hypothesized to play a relevant role in COVID-19, representing a strong defender against SARS-CoV-2 infection. The aim of our work was the study of immunohistochemical surfactant expression in the lungs of patients died following SARS-CoV-2 ARDS, in order to shed light on a possible therapeutic surfactant administration. PATIENTS AND METHODS: We investigated four patients who died due to ARDS following SARS-COV-2 infection and four patients submitted to lung biopsy, in the absence of SARS-CoV-2 infection. In all 8 cases, lung specimens were immunostained with anti-surfactant protein A (SP-A) and B (SP-B). RESULTS: In control subjects, reactivity for SP-B was restricted to type II alveolar cells. Immunostaining for SP-A was observed on the surface of alveolar spaces. In the COVID-19 positive lungs, immunoreactivity for SP-B was similar to that observed in control lungs; SP-A was strongly expressed along the alveolar wall. Moreover, dense aggregates of SP-A positive material were observed in the alveolar spaces. CONCLUSIONS: Our immunohistochemical data show the dysregulation of surfactant production in COVID-19 patients, particularly regarding SP-A expression. The increased presence of SP-A in condensed masses inside alveolar spaces could invalidate the therapeutic efficacy of the treatment with exogenous surfactant.
Assuntos
COVID-19/metabolismo , Imuno-Histoquímica , Precursores de Proteínas/análise , Proteína A Associada a Surfactante Pulmonar/análise , Proteínas Associadas a Surfactantes Pulmonares/análise , COVID-19/diagnóstico por imagem , Humanos , Precursores de Proteínas/genética , Precursores de Proteínas/metabolismo , Alvéolos Pulmonares/diagnóstico por imagem , Alvéolos Pulmonares/metabolismo , Proteína A Associada a Surfactante Pulmonar/genética , Proteína A Associada a Surfactante Pulmonar/metabolismo , Proteínas Associadas a Surfactantes Pulmonares/genética , Proteínas Associadas a Surfactantes Pulmonares/metabolismo , Estudos Retrospectivos , SARS-CoV-2/isolamento & purificação , SARS-CoV-2/metabolismoRESUMO
OBJECTIVE: Wilson's Disease (WD) is an autosomal recessive copper overload. Several mutations of the copper pump named ATP7B have been involved. WD is difficult to diagnose mainly because of its heterogeneity of presentation. The histologic spectrum is wide and not specific, ranging from very mild changes to severe disease. The histological picture of WD may overlap different conditions, including ALD, NAFLD, viral hepatitis or autoimmune liver disease. PATIENTS AND METHODS: We describe our experience on WD based on a single-center series of liver biopsies. One-hundred twenty-seven liver samples from 43 Sardinian WD patients were reviewed. The most reported pattern was steatohepatitis, accounting 82/127 biopsies (64.6%), followed by hepatitis in 25 biopsies (19.7%), and steatosis in 20 biopsies (15.7%). RESULTS: As for the elementary lesions, inflammation, steatosis, glycogenated nuclei and ballooning were the most frequent, being found in 107, 102, 90 and 86 biopsies out of the 127. Notably, all these lesions showed a predominant periportal location. There was no significant difference in the diagnostic pattern or in each elementary lesion between the biopsies performed at presentation and those performed during the follow-up. Lipogranuloma (significantly more numerous in the follow-up biopsies) and fibrosis (likewise significantly progressed in follow-up biopsies) were the only exceptions. CONCLUSIONS: Our data confirm the variability of the histological pattern in WD. However, the preferential localization of steatosis and balloon cells in periportal zone can be a useful clue for the diagnosis of WD.
Assuntos
Degeneração Hepatolenticular/diagnóstico , Fígado/patologia , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
OBJECTIVE: Colorectal cancer (CRC) is a complicated tumor, involving several oncogenic signaling pathways, and with a molecular mechanism not fully understood yet. The implication of thymosin ß4 (Tß4) with tumor insurgence and in migration of CRC cells was evidenced in the past with different methodologies, while Tß10 connection with CRC has been sporadically investigated. This study focused on the implication of both types of thymosin in CRC progression and invasion by analyzing the changes in their levels according to different zones of the tumor, and to Dukes stage and budding index. PATIENTS AND METHODS: Tß4 and Tß10 were analyzed in deep and superficial tumor samples, and normal mucosa from 18 patients. Concentrations of Tß4 and Tß10 have been measured by high-pressure liquid chromatography (HPLC) coupled to electrospray-ion trap mass spectrometry (ESI-IT-MS). MS data were compared by t-test and ANOVA statistical analysis. Identification of thymosin and their proteoforms has been performed by HPLC-high resolution-ESI-IT-MSMS. RESULTS: Both Tß4 and Tß10, exhibited intra-tumoral quantitative differences, being upregulated in the deep part of the CRC. They exhibited, moreover, strong association with the Dukes stage and the budding grade, being more concentrated in patients at Dukes stage B and with budding index "2". CONCLUSIONS: The results obtained in the present investigation encouraged the hypothesis that the two thymosin are involved in colorectal cancer progression, and in promoting cancer invasion. Thus, they are good candidates to be diagnostic/prognostic biomarkers and therapy targets.