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Background: The "classic" thyroid gland arterial vascularization takes into account two superior thyroid arteries (STA), two inferior thyroid arteries (ITA) and, occasionally, a thyroid ima artery (TIMA). The present review focuses on exploring the available data concerning thyroid gland arterial vascularization and its variations. Methods: Here, we analysed 49 articles from the last century, ranging from case reports to reviews concerning cadaver dissection classes, surgical intervention, and non-invasive techniques as well. Results: The harvested data clearly highlighted that: (i) the STA originates predominantly from the external carotid artery; (ii) the ITA is a branch of the thyrocervical trunk; and (iii) the TIMA is a very uncommon variant predominantly occurring to compensate for ITA absence. Conclusion: A systematic review of a highly vascularized organ is of great relevance during surgical intervention and, thus, the knowledge of normal anatomy and its modification is essential both for fact-finding and in surgery.
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Arterias , Glándula Tiroides , Cadáver , Humanos , Neovascularización Patológica , Glándula Tiroides/cirugíaRESUMEN
Cadmium (Cd) is a highly toxic environmental pollutant released from the smelting and refining of metals and cigarette smoking. Oral exposure to cadmium may result in adverse effects on a number of tissues, including the central nervous system (CNS). In fact, its toxicity has been related to neurological disorders, as well as neurodegenerative diseases such as Alzheimer's and Parkinson's diseases. Under normal conditions, Cd barely reaches the brain in adults because of the presence of the blood-brain barrier (BBB); however, it has been demonstrated that Cd-dependent BBB alteration contributes to pathogenesis of neurodegeneration. However, the mechanism underlying Cd-dependent BBB alteration remain obscure. Here, we investigated the signaling pathway of Cd-induced tight junction (TJ), F-actin, and vimentin protein disassembly in a rat brain endothelial cell line (RBE4). RBE4 cells treated with 10 µM cadmium chloride (CdCl2) showed a dose- and time-dependent significant increase in reactive oxygen species (ROS) production. This phenomenon was coincident with the alteration of the TJ zonula occludens-1 (ZO-1), F-actin, and vimentin proteins. The Cd-dependent ROS increase elicited the upregulation of GRP78 expression levels, a chaperone involved in endoplasmic reticulum (ER) stress that induces caspase-3 activation. Further signal profiling by the pannexin-1 (PANX1) specific inhibitor 10Panx revealed a PANX1-independent increase in ATP spillage in Cd-treated endothelial cells. Our results point out that a ROS-dependent ER stress-mediated signaling pathway involving caspase-3 activation and ATP release is behind the BBB morphological alterations induced by Cd.
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Barrera Hematoencefálica/metabolismo , Cadmio/metabolismo , Uniones Estrechas/metabolismo , Proteína de la Zonula Occludens-1/metabolismo , Actinas/metabolismo , Animales , Barrera Hematoencefálica/citología , Línea Celular , Estrés del Retículo Endoplásmico , Células Endoteliales/citología , Células Endoteliales/metabolismo , Ratas , Especies Reactivas de Oxígeno/metabolismo , Vimentina/metabolismoRESUMEN
Oxaliplatin-based regimens are effective in metastasized advanced cancers. However, a major limitation to their widespread use is represented by neurotoxicity that leads to peripheral neuropathy. In this study we evaluated the roles of a proven immunotherapeutic agent [Gc-protein-derived macrophage activating factor (GcMAF)] in preventing or decreasing oxaliplatin-induced neuronal damage and in modulating microglia activation following oxaliplatin-induced damage. The effects of oxaliplatin and of a commercially available formula of GcMAF [oleic acid-GcMAF (OA-GcMAF)] were studied in human neurons (SH-SY5Y cells) and in human microglial cells (C13NJ). Cell density, morphology and viability, as well as production of cAMP and expression of vascular endothelial growth factor (VEGF), markers of neuron regeneration [neuromodulin or growth associated protein-43 (Gap-43)] and markers of microglia activation [ionized calcium binding adaptor molecule 1 (Iba1) and B7-2], were determined. OA-GcMAF reverted the damage inflicted by oxaliplatin on human neurons and preserved their viability. The neuroprotective effect was accompanied by increased intracellular cAMP production, as well as by increased expression of VEGF and neuromodulin. OA-GcMAF did not revert the effects of oxaliplatin on microglial cell viability. However, it increased microglial activation following oxaliplatin-induced damage, resulting in an increased expression of the markers Iba1 and B7-2 without any concomitant increase in cell number. When neurons and microglial cells were co-cultured, the presence of OA-GcMAF significantly counteracted the toxic effects of oxaliplatin. Our results demonstrate that OA-GcMAF, already used in the immunotherapy of advanced cancers, may significantly contribute to neutralizing the neurotoxicity induced by oxaliplatin, at the same time possibly concurring to an integrated anticancer effect. The association between these two powerful anticancer molecules would probably produce the dual effect of reduction of oxaliplatin-induced neurotoxicity, together with possible synergism in the overall anticancer effect.
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Antineoplásicos/efectos adversos , Factores Activadores de Macrófagos/farmacología , Neuronas/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Compuestos Organoplatinos/efectos adversos , Proteína de Unión a Vitamina D/farmacología , Apoptosis/efectos de los fármacos , Antígeno B7-2/metabolismo , Proteínas de Unión al Calcio , Línea Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Técnicas de Cocultivo , AMP Cíclico/metabolismo , Proteínas de Unión al ADN/metabolismo , Proteína GAP-43/metabolismo , Humanos , Proteínas de Microfilamentos , Microglía/efectos de los fármacos , Neuronas/metabolismo , Neuronas/patología , Oxaliplatino , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
Growing evidence has shown the promise of mesenchymal stromal cells (MSCs) for the treatment of cutaneous wound healing. We have previously demonstrated that MSCs seeded on an artificial dermal matrix, Integra (Integra Lifesciences Corp., Plainsboro, NJ) enriched with platelet-rich plasma (Ematrix) have enhanced proliferative potential in vitro as compared with those cultured on the scaffold alone. In this study, we extended the experimentation by evaluating the efficacy of the MSCs seeded scaffolds in the healing of skin wounds in an animal model in vivo. It was found that the presence of MSCs within the scaffolds greatly ameliorated the quality of regenerated skin, reduced collagen deposition, enhanced reepithelization, increased neo-angiogenesis, and promoted a greater return of hair follicles and sebaceous glands. The mechanisms involved in these beneficial effects were likely related to the ability of MSCs to release paracrine factors modulating the wound healing response. MSC-seeded scaffolds, in fact, up-regulated matrix metalloproteinase 9 expression in the extracellular matrix and enhanced the recruitment of endogenous progenitors during tissue repair. In conclusion, the results of this study provide evidence that the treatment with MSC-seeded scaffolds of cutaneous wounds contributes to the recreation of a suitable microenvironment for promoting tissue repair/regeneration at the implantation sites.
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Matriz Extracelular/patología , Trasplante de Células Madre Mesenquimatosas/métodos , Células Madre Mesenquimatosas/metabolismo , Piel/fisiopatología , Ingeniería de Tejidos , Cicatrización de Heridas , Heridas y Lesiones/fisiopatología , Animales , Diferenciación Celular , Células Cultivadas , Modelos Animales de Enfermedad , Masculino , Ratas , Regeneración , Piel/lesionesRESUMEN
Quality by Design (QbD) is a new paradigm of quality to be applied to pharmaceutical products and processes, recently encouraged by International Conference on Harmonisation guidelines. In this paper QbD approach was applied to the development of a CE method for the simultaneous assay of metformin hydrochloride (MET) and its main impurities. QbD strategy was focused on electrophoretic process understanding, and the analytical method was thoroughly evaluated by applying risk assessment and chemometric tools. Method scouting allowed CD-CZE based on the addition of carboxymethyl-ß-CD to Britton-Robinson acidic buffer to be chosen as operative mode. Seven critical process parameters (CPPs) were selected, related to capillary, injection, BGE and instrumental settings. The effect of the different levels of the CPPs on critical quality attributes (CQAs), e.g. critical resolution values and analysis time, was evaluated in a screening study. Response surface methodology led to draw contour plots and sweet spot plots. The definition of design space was accomplished by applying Monte-Carlo simulations, thus identifying by risk of failure maps a multivariate zone where the CQAs fulfilled the requirements with a selected probability. Finally, a control strategy was designed and the method was applied to a real sample of MET tablets.
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Ciclodextrinas/química , Electroforesis Capilar/métodos , Metformina/análisis , Contaminación de Medicamentos , Metformina/análogos & derivados , Metformina/química , Reproducibilidad de los Resultados , Proyectos de Investigación , Comprimidos/químicaRESUMEN
Knowledge of anatomical variability is extremely important in order to better understand the etiology of pain, if present, or to avoid iatrogenic consequences. Sometimes the anatomical "anomalies" have the same anamnesis but different causes. For example, sciatic neuralgia may be caused by a herniated disc or it may have a different origin. The sciatic nerve (SN), also known as the ischial nerve, is the widest in the human body. This huge peripheral nerve originates from the roots of the lumbosacral plexus (L4-S3) and passes through the great sciatic foramen, under the piriformis muscle (PM). However, there is much variability in the pattern of SNs about the muscle, which has been known since the first half of the 20th century. In the present study, we describe six different case reports of anatomical variations of the SN and its interplay with the PM. The observations were made during dissection classes at the ICLO Teaching and Research Centre (Verona, Italy), on both male and female cadavers aged between 58 and 84 years. The SN was reported as a single and divided nerve into the tibial nerve (TN) and the common peroneal nerve (CPN), passing alone above, below, or between the PM. However, the two parts of the SN may also interact with the PM in different ways, adding to the anatomical variability. A thorough knowledge of the anatomical variations in any part of the human body is extremely important. The various techniques used, from imaging to autopsy or surgery, are also useful in the SN pathway. Thus, the anatomical features and the understanding of each variation are useful for a correct approach that can lead to an effective and correct treatment with a favorable outcome.
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Anatomical variability in the human body is not as rare as was previously hypothesised. Indeed, as recently reviewed, the term 'norm' in anatomy can be considered an approximation. Thus, anatomical variations occur quite often, as largely demonstrated during non-invasive diagnosis, surgical intervention, or post mortem investigations. In the present study, we describe different anatomical variations in both the right and left lungs derived from cadavers of different ethnicities. The analysed organs were collected during dissection, and accessory lobes and fissures were observed in both the right and left lungs. Moreover, a horizontal fissure was missing from the right lung, resulting in only two lobes. Since lung anatomical variability is common in clinical practice and preclinical imaging studies can miss different morphologies, a deep and accurate knowledge of the anatomical variations of the lung is of extreme importance to avoid difficulties or changes during the surgical procedure.
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Cuerpo Humano , Pulmón , Humanos , Animales , Pulmón/anatomía & histología , Cadáver , Autopsia/veterinaria , Disección/veterinariaRESUMEN
All allergic responses to food indicate the failure of immunological tolerance, but it is unclear why cow's milk and egg (CME) allergies resolve more readily than reactivity to peanuts (PN). We sought to identify differences between PN and CME allergies through constitutive immune status and responses to cognate and non-cognate food antigens. Children with confirmed allergy to CME (n = 6) and PN (n = 18) and non-allergic (NA) (n = 8) controls were studied. Constitutive secretion of cytokines was tested in plasma and unstimulated mononuclear cell (PBMNC) cultures. Blood dendritic cell (DC) subsets were analyzed alongside changes in phenotypes and soluble molecules in allergen-stimulated MNC cultures with or without cytokine neutralization. We observed that in allergic children, constitutively high plasma levels IL-1ß, IL-2, IL-4, IL-5 and IL-10 but less IL-12p70 than in non-allergic children was accompanied by the spontaneous secretion of sCD23, IL-1ß, IL-2, IL-4, IL-5, IL-10, IL-12p70, IFN-γ and TNF-α in MNC cultures. Furthermore, blood DC subset counts differed in food allergy. Antigen-presenting cell phenotypic abnormalities were accompanied by higher B and T cell percentages with more Bcl-2 within CD69+ subsets. Cells were generally refractory to antigenic stimulation in vitro, but IL-4 neutralization led to CD152 downregulation by CD4+ T cells from PN allergic children responding to PN allergens. Canonical discriminant analyses segregated non-allergic and allergic children by their cytokine secretion patterns, revealing differences and areas of overlap between PN and CME allergies. Despite an absence of recent allergen exposure, indication of in vivo activation, in vitro responses independent of challenging antigen and the presence of unusual costimulatory molecules suggest dysregulated immunity in food allergy. Most importantly, higher Bcl-2 content within key effector cells implies survival advantage with the potential to mount abnormal responses that may give rise to the manifestations of allergy. Here, we put forward the hypothesis that the lack of apoptosis of key immune cell types might be central to the development of food allergic reactions.
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Hipersensibilidad a los Alimentos , Hipersensibilidad a la Leche , Niño , Femenino , Animales , Bovinos , Humanos , Interleucina-10 , Interleucina-4 , Interleucina-5/metabolismo , Interleucina-2 , Alérgenos , Citocinas/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2RESUMEN
With the recent advances in medicine, human life expectancy is increasing; however, the extra years of life are not necessarily spent in good health or free from disability, resulting in a significantly higher incidence of age-associated pathologies. Among these disorders, neurodegenerative diseases have a significant impact. To this end, the presence of the protective blood-brain barrier (BBB) represents a formidable obstacle to the delivery of therapeutics. Thus, this makes it imperative to define strategies to bypass the BBB in order to successfully target the brain with the appropriate drugs. It has been demonstrated that targeting the BBB by ultrasound (US) can transiently make this anatomical barrier permeable and in so doing, allow the delivery of therapeutics. Thus, our aim was to carry out an in depth in vitro molecular and morphological study on the effects of US treatment on the BBB. The rat brain endothelial (RBE4) cell line was challenged with exposure to 12 MHz diagnostic US treatment for 10, 20, and 30 min. Cell viability assays, Western blotting analysis on the endoplasmic reticulum (ER), and oxidative stress marker evaluation were then performed, along with cytological and immunofluorescence staining, in order to evaluate the effects of US on the intercellular spaces and tight junction distribution of the brain endothelial cells. We observed that the US treatment exerted no toxic effects on either RBE4 cell viability or the upregulation/dislocation of the ER and oxidative stress marker (GRP78 and cytochrome C, respectively). Further, we observed that the application of US induced an increase in the intercellular spaces, as shown by Papanicolaou staining, mainly due to the altered distribution of the tight junction protein zonula occludens-1 (ZO-1). This latter US-dependent effect was transient and disappeared 20 min after the removal of the stimulus. In conclusion, our results show that US induces a transient alteration of the BBB, without altering the intracellular signaling pathways such as the ER and oxidative stress that could potentially be toxic for endothelial cells. These results suggested that US treatment could represent a potential strategy for improving drug delivery to the brain.
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Barrera Hematoencefálica , Células Endoteliales , Ratas , Animales , Humanos , Barrera Hematoencefálica/patología , Células Endoteliales/metabolismo , Encéfalo/metabolismo , Línea Celular , Uniones Estrechas/metabolismoRESUMEN
BACKGROUND: Temporomandibular joint (TMJ) disorders, which affect millions of people worldwide, have multiple etiological factors that make an accurate diagnosis and effective treatments difficult. As a consequence, the gold standard diagnostic criteria for TMJ disorders remain elusive and often depend on subjective decisions. AIM: In this context, the lack of a non-invasive quantitative methodology capable of assessing the functional physiological state and, consequently, identifying risk indicators for the early diagnosis of TMJ disorders must be tackled and resolved. METHODOLOGY: In this work, we have studied the biomechanics and viscoelastic properties of the functional masticatory system by a non-invasive approach involving 52 healthy subjects, analysed by statistical-physics analysis applied to myotonic measurements on specific points of the masticatory system designing a TMJ network composed of 17 nodes and 20 links. RESULTS: We find that the muscle tone and viscoelasticity of a specific cycle linking frontal, temporal, and mandibular nodes of the network play a prominent role in the physiological functionality of the system. At the same time, the functional state is characterised by a landscape of nearly degenerated levels of elasticity in all links of the network, making this parameter critically distributed and deviating from normal behaviour. CONCLUSIONS: Time evolution and dynamic correlations between biomechanics and viscoelastic parameters measured on the different cycles of the network provide a quantitative framework associated with the functional state of the masticatory system. Our results are expected to contribute to enriching the taxonomy of this system, primarily based on clinical observations, patient symptoms, and expert consensus.
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INTRODUCTION: For many years, anatomical studies have been conducted with a shattered view of the body. Although the study of the different apparatuses provides a systemic view of the human body, the reconstruction of the complex network of anatomical structures is crucial for the understanding of structural and functional integration. AIM: We used network analysis to investigate the connection between the whole-body osteo-myofascial structures of the human musculoskeletal system. MATERIALS AND METHODS: The musculoskeletal network was performed using the aNETomy® anatomical network with the implementation of the open-source software Cytoscape for data entry. RESULTS: The initial graph was applied with a network consisting of 2298 body parts (nodes) and 7294 links, representing the musculoskeletal system. Considering the same weighted and unweighted osteo-myofascial network, a different distribution was obtained, suggesting both a topological organization and functional behavior of the network structure. CONCLUSIONS: Overall, we provide a deeply detailed anatomical network map of the whole-body musculoskeletal system that can be a useful tool for the comprehensive understanding of every single structure within the complex morphological organization, which could be of particular interest in the study of rehabilitation of movement dysfunctions.
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Cadmium (Cd) is a well-known occupational and environmental pollutant worldwide, and its toxicity is widely recognised. Cd is reported to increase the permeability of the blood-brain barrier (BBB) and to penetrate and accumulate in the brain. Although many lines of evidence show that Cd toxicity is induced by different mechanisms, one of the best known is the Cd-dependent production of reactive oxygen species (ROS). Zinc is a trace element known as coenzyme and cofactor for many antioxidant proteins, such as metallothioneins and superoxide dismutase enzymes. To date, very little is known about the role of Zn in preventing Cd-induced blood-brain barrier (BBB) alterations. The goal of this study was to test the Zn antioxidant capacity against Cd-dependent alterations in a rat brain endothelial cell line (RBE4), as an in vitro model for BBB. In order to mimic acute Cd poisoning, RBE4 cells were treated with CdCl2 30 µM for 24 h. The protective role of ZnCl2 (50 µM) was revealed by evaluating the cell viability, reactive oxygen species (ROS) quantification, cytochrome C distribution, and the superoxide dismutase (SOD) protein activity. Additionally, the effectiveness of Zn in counteracting the Cd-induced damage was investigated by evaluating the expression levels of proteins already known to be involved in the Cd signalling pathway, such as GRP78 (an endoplasmic reticulum (ER) stress protein), caspase3 pro- and cleaved forms, and BAX. Finally, we evaluated if Zn was able to attenuate the alterations of zonula occludens-1 (ZO-1), one of the tight-junction (TJ) proteins involved in the formation of the BBB. Our data clearly demonstrate that Zn, by protecting from the SOD activity impairment induced by Cd, is able to prevent the triggering of the Cd-dependent signalling pathway that leads to ZO-1 dislocation and downregulation, and BBB damage.
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Cadmio , Zinc , Animales , Antioxidantes/metabolismo , Barrera Hematoencefálica/metabolismo , Cadmio/metabolismo , Cadmio/toxicidad , Ratas , Especies Reactivas de Oxígeno/metabolismo , Superóxido Dismutasa/metabolismo , Zinc/metabolismo , Zinc/farmacologíaRESUMEN
BACKGROUND: Natural surfactant combined with beclomethasone decreases pulmonary oxidative stress in preterm lambs with respiratory distress syndrome (RDS). OBJECTIVES: To test the hypothesis that this occurs through a decrease in pulmonary inflammation. METHODS: Preterm lambs received 200 mg/kg of natural surfactant or 200 mg/kg of natural surfactant combined with 400 or 800 µg/kg of beclomethasone. Interleukin 8 (IL-8) and macrophage migration inhibitory factor (MIF) were assayed in bronchial aspirate samples and lung mechanics were evaluated. RESULTS: IL-8 increased in all the groups, but the increase was lower in the groups treated with surfactant plus 400 and 800 µg/kg of beclomethasone. MIF decreased in the surfactant group, did not vary in the surfactant plus 400 µg/kg beclomethasone group, and decreased in the surfactant plus 800 µg/kg beclomethasone group. MIF concentration was higher in the surfactant plus 800 µg/kg beclomethasone group than in the other groups. CONCLUSIONS: Natural surfactant combined with beclomethasone at 800 µg/kg is effective in reducing lung inflammation in an animal model of RDS, thus explaining the associated decrease in lung oxidative stress. The increase in MIF in animals treated with surfactant plus 800 µg/kg of beclomethasone might be an important maturative and protective factor for neonatal lungs.
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Antiinflamatorios/farmacología , Beclometasona/farmacología , Factores Inhibidores de la Migración de Macrófagos/farmacología , Estrés Oxidativo/efectos de los fármacos , Neumonía/tratamiento farmacológico , Surfactantes Pulmonares/metabolismo , Síndrome de Dificultad Respiratoria del Recién Nacido/tratamiento farmacológico , Animales , Animales Recién Nacidos , Antiinflamatorios/administración & dosificación , Beclometasona/administración & dosificación , Modelos Animales de Enfermedad , Femenino , Humanos , Recién Nacido , Interleucina-8/efectos de los fármacos , Neumonía/patología , Embarazo , Surfactantes Pulmonares/farmacología , Síndrome de Dificultad Respiratoria del Recién Nacido/patología , OvinosRESUMEN
Oxaliplatin is a third-generation chemotherapy drug mainly used for colorectal cancer treatment. However, it is also known to trigger neuropathy whose underlying neurobiological mechanisms are still under investigation and currently available treatments show limited efficacy. It is now established that neurons are not the only cell type involved in chronic pain and that glial cells, mainly astrocytes and microglia, are involved in the initiation and maintenance of neuropathy. Among all the pathogenetic factors involved in neuropathic pain, an oxaliplatin-dependent oxidative stress plays a predominant role. In our study, the antioxidant properties of magnesium (Mg), manganese (Mn) and zinc (Zn) salts were evaluated in order to counteract microglial activation induced by oxaliplatin. The antioxidant efficacy of these metals was evaluated by the means of molecular and morphological assays on the BV-2 microglial cell line. Our data clearly show that Mg, Mn and Zn are able to prevent oxaliplatin-dependent microglial alterations by reducing both oxidative and endoplasmic reticulum stress.
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Antioxidantes/farmacología , Cloruros/farmacología , Cloruro de Magnesio/farmacología , Compuestos de Manganeso/farmacología , Oxaliplatino/toxicidad , Compuestos de Zinc/farmacología , Animales , Antígeno B7-2/metabolismo , Proteínas de Unión al Calcio/metabolismo , Línea Celular , Estrés del Retículo Endoplásmico/efectos de los fármacos , Ratones , Proteínas de Microfilamentos/metabolismo , Microglía/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismoRESUMEN
In recent years, alcohol abuse has dramatically grown with deleterious consequence for people's health and, in turn, for health care costs. It has been demonstrated, in humans and animals, that alcohol intoxication induces neuroinflammation and neurodegeneration thus leading to brain impairments. Furthermore, it has been shown that alcohol consumption is able to impair the blood-brain barrier (BBB), but the molecular mechanisms underlining this detrimental effect have not been fully elucidated. For this reason, in this study we investigated the effects of alcohol exposure on a rat brain endothelial (RBE4) cell line, as an in vitro-validated model of brain microvascular endothelial cells. To assess whether alcohol caused a concentration-related response, the cells were treated at different times with increasing concentrations (10-1713 mM) of ethyl alcohol (EtOH). Microscopic and molecular techniques, such as cell viability assay, immunofluorescence and Western blotting, were used to examine the mechanisms involved in alcohol-induced brain endothelial cell alterations including tight junction distribution, apoptosis, and reactive oxygen species production. Our findings clearly demonstrate that alcohol causes the formation of gaps between cells by tight junction disassembly, triggered by the endoplasmic reticulum and oxidative stress, highlighted by GRP78 chaperone upregulation and increase in reactive oxygen species production, respectively. The results from this study shed light on the mechanisms underlying alcohol-induced blood-brain barrier dysfunction and a better understanding of these processes will allow us to take advantage of developing new therapeutic strategies in order to prevent the deleterious effects of alcohol.
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Barrera Hematoencefálica , Células Endoteliales , Animales , Transporte Biológico , Encéfalo , Chaperón BiP del Retículo Endoplásmico , Especies Reactivas de Oxígeno/metabolismo , Uniones Estrechas/metabolismoRESUMEN
Hyaluronic acid fillers indisputably represent an important tool for face rejuvenation and volume restoration. The temporal area has recently been considered as a potential site of injection. As it happens in the middle face and in other regions of the face, the temporal fossa changes according to the aging process. In a young person, the temple profile has a fullness aspect, and this contributes to giving the face a beautiful and healthy appearance. With age, the loss of volume leads the bone prominences to be visible. The aim of this article is to classify the temporal fossa atrophy and get better into the anatomy, identifying the ideal plane to inject in, through the use of a safe and reliable technique. Cadaver dissections have been performed to specifically describe the anatomy of the temple layer by layer. The authors' preferred technique, called interfascial by cannula implantation, is discussed. All the treated patients reported a good improvement by survey according to the Global Aesthetic Improvement Scale scale. No major complications were detected. No ecchymosis neither swelling were documented. Although further studies are necessary to broaden the casuistry and better verify the potentiality of this technique, the authors do believe that it could be considered a very reliable procedure with pretty consistent results, if supported by an adequate and imperative anatomical knowledge.
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Cadmium (Cd), a category I human carcinogen, is a well-known widespread environmental pollutant. Chronic Cd exposure affects different organs and tissues, such as the central nervous system (CNS), and its deleterious effects can be linked to indirect reactive oxygen species (ROS) generation. Since Cd is predominantly present in +2 oxidation state, it can interplay with a plethora of channels and transporters in the cell membrane surface in order to enter the cells. Mitochondrial dysfunction, ROS production, glutathione depletion and lipid peroxidation are reviewed in order to better characterize the Cd-elicited molecular pathways. Furthermore, Cd effects on different CNS cell types have been highlighted to better elucidate its role in neurodegenerative disorders. Indeed, Cd can increase blood-brain barrier (BBB) permeability and promotes Cd entry that, in turn, stimulates pericytes in maintaining the BBB open. Once inside the CNS, Cd acts on glial cells (astrocytes, microglia, oligodendrocytes) triggering a pro-inflammatory cascade that accounts for the Cd deleterious effects and neurons inducing the destruction of synaptic branches.
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Although modern anatomy is commonly retained to begin in the XVI century, the roots of anatomical study in the Western world may be identified beforehand. An anatomical practice was present in the Western world well before the Middle Ages, starting in ancient Greece. Hippocrates of Cos (V-IV centuries B.C.) provided descriptions of the heart and vessels, and the so-called "Hippocratic Corpus" largely deals with anatomy. Aristotle of Stagira (IV century B.C.) was one of the first well-known scholars of the past to perform dissections of animals. The anatomical interest of Aristotle contained a "physiological" background too, since he was convinced that all parts of human organisms had one or more specific functions. Galen of Pergamum (II century A.D.) was the performer of hundreds of dissections of animals, and he described a great number of anatomical parts of apes, dogs, goats and pigs. The anatomical system of Galen became a gold standard for medicine for more than a thousand years, and in the Middle Ages (V-XV centuries A.D.) the human anatomy that was taught and acquired in European universities remained based on Galenic anatomy. In conclusion, Greek-speaking scholars between the IV century B.C. and the II century A.D. set the basis for the systematic dissection of animals and the comparative investigation of animal anatomical findings. These scholars also began to study the structures of the human body, interestingly taking into account the relationship between the macroscopical morphology of observed structures and their more evident functions. (www.actabiomedica.it).
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Anatomía/historia , Anatomía/educación , Animales , Historia Antigua , Humanos , Mundo OccidentalRESUMEN
Oxaliplatin is a key drug in the treatment of advanced metastatic colorectal cancer. Despite its beneficial effects in tumor reduction, the most prevalent side-effect of oxaliplatin treatment is a chemotherapy-induced neuropathy that frequently forces to discontinue the therapy. Indeed, along with direct damage to peripheral nerves, the chemotherapy-related neurotoxicity involves also the central nervous system (CNS) as demonstrated by pain chronicity and cognitive impairment (also known as chemobrain), a newly described pharmacological side effect. The presence of the blood brain barrier (BBB) is instrumental in preventing the entry of the drug into the CNS; here we tested the hypothesis that oxaliplatin might enter the endothelial cells of the BBB vessels and trigger a signaling pathway that induce the disassembly of the tight junctions, the critical components of the BBB integrity. By using a rat brain endothelial cell line (RBE4) we investigated the signaling pathway that ensued the entry of oxaliplatin within the cell. We found that the administration of 10 µM oxaliplatin for 8 and 16 h induced alterations of the tight junction (TJs) proteins zonula occludens-1 (ZO-1) and of F-actin, thus highlighting BBB alteration. Furthermore, we reported that intracellular oxaliplatin rapidly induced increased levels of reactive oxygen species and endoplasmic reticulum stress, assessed by the evaluation of glucose-regulated protein GRP78 expression levels. These events were accompanied by activation of caspase-3 that led to extracellular ATP release. These findings suggested a possible novel mechanism of action for oxaliplatin toxicity that could explain, at least in part, the chemotherapy-related central effects.
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Cadmium (Cd), a worldwide occupational pollutant, is an extremely toxic heavy metal, capable of damaging several organs, including the brain. Its toxicity has been related to neurodegenerative diseases such as Alzheimer's and Parkinson's diseases. The neurotoxic potential of Cd has been attributed to the changes induced in the brain enzyme network involved in counteracting oxidative stress. On the other hand, it is also known that trace elements, such as zinc (Zn) and selenium (Se), required for optimal brain functions, appears to have beneficial effects on the prevention of Cd intoxication. Based on this protective effect of Zn and Se, we aimed to investigate whether these elements could protect neuronal cells from Cd-induced excitotoxicity. The experiments, firstly carried out on SH-SY5Y catecholaminergic neuroblastoma cell line, demonstrated that the treatment with 10⯵M cadmium chloride (CdCl2) for 24â¯h caused significant modifications both in terms of oxidative stress and neuronal sprouting, triggered by endoplasmic reticulum (ER) stress. The evaluation of the effectiveness of 50⯵M of zinc chloride (ZnCl2) and 100â¯nM sodium selenite (Na2SeO3) treatments showed that both elements were able to attenuate the Cd-dependent neurotoxicity. However, considering that following induction with retinoic acid (RA), the neuroblastoma cell line undergoes differentiation into a cholinergic neurons, our second aim was to verify the zinc and selenium efficacy also in this neuronal phenotype. Our data clearly demonstrated that, while zinc played a crucial role on neuroprotection against Cd-induced neurotoxicity independently from the cellular phenotype, selenium is ineffective in differentiated cholinergic cells, supporting the notion that the molecular events occurring in differentiated SH-SY5Y cells are critical for the response to specific stimuli.