13 results on '"Balaskas N"'
Search Results
2. The gene regulatory logic of Shh morphogen interpretation in the ventral neural tube
- Author
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Balaskas, N.
- Subjects
571.8 - Abstract
During development, many signaling molecules function as morphogens, long-range signals, to provide positional information that directs the pattern of cellular differentiation. One such signal, Sonic Hedgehog (Shh), patterns the dorso-ventral (D/V) axis of the neural tube by controlling the expression of transcription factors in progenitor cells. One such factor is Nkx2.2, which is expressed in response to high levels and prolonged periods of Shh signaling. Analysis of the regulatory elements controlling Nkx2.2 has revealed a 250bp evolutionary conserved region (ECR), sufficient to drive Nkx2.2 expression. Among other transcription factor binding sites, this element contains a Gli‐binding site (GBS), necessary for Nkx2.2 expression. Mutational analysis suggests that the affinity and/or number of GBSs determine the level but not the spatial domain of Nkx2.2 expression pattern. Instead, correct Nkx2.2 expression requires both positive and negative inputs from other transcription factors. These factors are part of a transcriptional network that restricts Nkx2.2 expression in the p3 domain. One part of this network consisting of Pax6 and Olig2 determines the dorsal limit of Nkx2.2 expression, while a second part consisting of FoxA2, FoxP2 and FoxP4 determines the ventral limit of expression of Nkx2.2 domain. These transcription factors also appear to determine the temporal features of Nkx2.2 expression in the neural tube. Furthermore, sequence analysis identified a potential Fox binding motif within a 10bp region of the ECR that appears to control the ventral limit of Nkx2.2 expression. Together these data are consistent with a model in which the combination of Shh signaling and downstream transcriptional network generates the spatiotemporal profile of Nkx2.2 expression.
- Published
- 2010
3. The anti-inflammatory effects of aerobic exercise training in patients with type 2 diabetes: A systematic review and meta-analysis.
- Author
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Papagianni G, Panayiotou C, Vardas M, Balaskas N, Antonopoulos C, Tachmatzidis D, Didangelos T, Lambadiari V, and Kadoglou NPE
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- Adult, Humans, Interleukin-6, Adiponectin, C-Reactive Protein analysis, Tumor Necrosis Factor-alpha therapeutic use, Anti-Inflammatory Agents therapeutic use, Biomarkers, Resistin, Diabetes Mellitus, Type 2 drug therapy
- Abstract
Background: Type 2 diabetes mellitus (T2DM) is a low-grade, chronic inflammatory disease, associated with increased cardiovascular risk. The purpose of this systematic review/ meta-analysis was to evaluate the effects of aerobic exercise training (AET) on inflammatory markers in T2DM patients., Methods: The literature search was conducted utilizing PubMed, Web of Science, Embase, and the Cochrane Library from their inception up to April 2022. We screened only for randomized controlled trials (RCTs) investigating the effects of AET on C-reactive protein (CRP) and adipokines: adiponectin, resistin, interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-a), along with changes in anthropometric indices and glycemic control in adult T2DM patients. Pooled post-exercise weighted mean differences (WMDs) with 95% Confidence Intervals (CIs) were calculated for all outcomes of interest between exercise-treated patients and controls., Results: Twenty-six RCTs involving 1239 T2DM patients were retrieved from the databases for meta-analysis. The cumulative results showed that post-AET inflammatory markers were lower in exercise-treated patients compared to controls regarding CRP (mg/L): WMD: -0.91; 95%CIs: -1.43, -0.40; p < 0.001 resistin (mg/ml): (WMD: -2.08; 95%CIs: -3.32, -0.84; p < 0.001); TNF-a (pg/ml): (WMD: -2.70; 95%CIs: -4.26, -1.14; p < 0.001), and IL-6 (pg/ml): (WMD: -1.05; 95%CIs: -1.68, -0.43; p < 0.001). Those effects were accompanied by significant amelioration of fasting glucose (mg/dl) (WMD: -13.02; 95%CIs: -25.39, -0.66; p = 0.04), HbA1c (%) (WMD: -0.51; 95%CIs: -0.73, -0.28, p < 0.001), and fat mass (%) (WMD: -3.14; 95%CI: -4.71, -1.58; p < 0.001). Our meta-analysis demonstrated less-consistent results for adiponectin (μg/ml), (WMD: 1.00; 95%CI: -0.12, 2.12; p = 0.08) and body-mass index (kg/m
2 ) (WMD: -1.34; 95%CI: -2.76, 0.08; p = 0.06) tending to differ between AET and control group., Conclusions: AET can significantly reduce the inflammatory burden in T2DM patients. by ameliorating the circulating levels of CRP, resistin, TNF-a and IL-6, even without accompanied significant weight-loss. The clinical impact of those anti-inflammatory effects of AET needs to be determined., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)- Published
- 2023
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4. A Comprehensive Review of the Cardiovascular Protective Properties of Silibinin/Silymarin: A New Kid on the Block.
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Kadoglou NPE, Panayiotou C, Vardas M, Balaskas N, Kostomitsopoulos NG, Tsaroucha AK, and Valsami G
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Silibinin/silymarin has been used in herbal medicine for thousands of years and it is well-known for its hepato-protective properties. The present comprehensive literature review aimed to critically summarize the pharmacological properties of silymarin extract and its main ingredient silibinin in relation to classical cardiovascular risk factors (e.g., diabetes mellitus, etc.). We also assessed their potential protective and/or therapeutic application in cardiovascular diseases (CVDs), based on experimental and clinical studies. Pre-clinical studies including in vitro tests or animal models have predominantly implicated the following effects of silymarin and its constituents: (1) antioxidant, (2) hypolipidemic, (3) hypoglycemic, (4) anti-hypertensive and (5) cardioprotective. On the other hand, a direct amelioration of atherosclerosis and endothelial dysfunction after silymarin administration seems weak based on scarce data. In clinical trials, the most important findings are improved (1) glycemic and (2) lipid profiles in patients with type 2 diabetes mellitus and/or hyperlipidemia, while (3) the anti-hypertensive effects of silibinin/silymarin seem very modest. Finally, the changes in clinical endpoints are not robust enough to draw a firm conclusion. There are significant limitations in clinical trial design, including the great variety in doses and cohorts, the underlying conditions, the small sample sizes, the short duration and the absence of pharmacokinetic/pharmacodynamic tests prior to study commitment. More data from well-designed and high-quality pre-clinical and clinical studies are required to firmly establish the clinical efficacy of silibinin/silymarin and its possible therapeutic application in cardiovascular diseases.
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- 2022
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5. The Positional Logic of Sensory-Motor Reflex Circuit Assembly.
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Balaskas N, Ng D, and Zampieri N
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- Axon Guidance, Logic, Reflex, Motor Neurons, Spinal Cord
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Throughout his scientific career, Tom Jessell pioneered the spinal cord as a model system to study the molecular programs of neural specification, axon guidance, and connection specificity. His contributions to these fields and more broadly to that of developmental neuroscience will continue to inspire and define many generations of researchers. It is challenging to capture all of Tom's findings in one essay, and therefore, here we wish to briefly highlight his contributions to the problem of connection specificity, with a focus on the spinal sensory-motor reflex circuit. In particular, emphasis will be placed on discoveries from his laboratory that revealed a significant role of positional strategies in establishing selective sensory-motor connections. This work introduced novel principles of neuronal connectivity that may apply to how precise circuit wiring occurs throughout the nervous system., (Copyright © 2020 IBRO. Published by Elsevier Ltd. All rights reserved.)
- Published
- 2020
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6. Positional Strategies for Connection Specificity and Synaptic Organization in Spinal Sensory-Motor Circuits.
- Author
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Balaskas N, Abbott LF, Jessell TM, and Ng D
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- Animals, Axons, Buttocks, Dendrites, Foot, Hindlimb, Mice, Microscopy, Confocal, Motor Neurons cytology, Proprioception, Sensory Receptor Cells cytology, Spinal Cord anatomy & histology, Motor Neurons physiology, Muscle, Skeletal innervation, Sensory Receptor Cells physiology, Spinal Cord physiology, Synapses physiology
- Abstract
Proprioceptive sensory axons in the spinal cord form selective connections with motor neuron partners, but the strategies that confer such selectivity remain uncertain. We show that muscle-specific sensory axons project to motor neurons along topographically organized angular trajectories and that motor pools exhibit diverse dendritic arbors. On the basis of spatial constraints on axo-dendritic interactions, we propose positional strategies that can account for sensory-motor connectivity and synaptic organization. These strategies rely on two patterning principles. First, the degree of axo-dendritic overlap reduces the number of potential post-synaptic partners. Second, a close correlation between the small angle of axo-dendritic approach and the formation of synaptic clusters imposes specificity of connections when sensory axons intersect multiple motor pools with overlapping dendritic arbors. Our study identifies positional strategies with prominent roles in the organization of spinal sensory-motor circuits., (Copyright © 2019 Elsevier Inc. All rights reserved.)
- Published
- 2019
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7. Gene regulatory logic for reading the Sonic Hedgehog signaling gradient in the vertebrate neural tube.
- Author
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Balaskas N, Ribeiro A, Panovska J, Dessaud E, Sasai N, Page KM, Briscoe J, and Ribes V
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- Animals, Basic Helix-Loop-Helix Transcription Factors genetics, Eye Proteins genetics, Hedgehog Proteins genetics, Homeobox Protein Nkx-2.2, Homeodomain Proteins genetics, Homeodomain Proteins metabolism, Kruppel-Like Transcription Factors genetics, Kruppel-Like Transcription Factors metabolism, Mice, Mice, Transgenic, Nerve Tissue Proteins genetics, Nerve Tissue Proteins metabolism, Neural Stem Cells metabolism, Oligodendrocyte Transcription Factor 2, PAX6 Transcription Factor, Paired Box Transcription Factors genetics, Repressor Proteins genetics, Transcription Factors metabolism, Zebrafish Proteins, Zinc Finger Protein Gli3, Gene Regulatory Networks, Hedgehog Proteins metabolism, Neural Tube metabolism, Signal Transduction
- Abstract
Secreted signals, known as morphogens, provide the positional information that organizes gene expression and cellular differentiation in many developing tissues. In the vertebrate neural tube, Sonic Hedgehog (Shh) acts as a morphogen to control the pattern of neuronal subtype specification. Using an in vivo reporter of Shh signaling, mouse genetics, and systems modeling, we show that a spatially and temporally changing gradient of Shh signaling is interpreted by the regulatory logic of a downstream transcriptional network. The design of the network, which links three transcription factors to Shh signaling, is responsible for differential spatial and temporal gene expression. In addition, the network renders cells insensitive to fluctuations in signaling and confers hysteresis--memory of the signal. Our findings reveal that morphogen interpretation is an emergent property of the architecture of a transcriptional network that provides robustness and reliability to tissue patterning., (Copyright © 2012 Elsevier Inc. All rights reserved.)
- Published
- 2012
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8. Sox1 maintains the undifferentiated state of cortical neural progenitor cells via the suppression of Prox1-mediated cell cycle exit and neurogenesis.
- Author
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Elkouris M, Balaskas N, Poulou M, Politis PK, Panayiotou E, Malas S, Thomaidou D, and Remboutsika E
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- Animals, Bromodeoxyuridine analysis, Cell Cycle genetics, Cell Cycle physiology, Cell Division genetics, Cell Division physiology, Cells, Cultured, Embryonic Stem Cells cytology, Embryonic Stem Cells physiology, Gene Knock-In Techniques, Homeodomain Proteins genetics, Immunohistochemistry, Mice, Mice, Mutant Strains, Neural Stem Cells cytology, Neurogenesis genetics, SOXB1 Transcription Factors genetics, Tumor Suppressor Proteins genetics, Homeodomain Proteins physiology, Neural Stem Cells physiology, Neurogenesis physiology, Neurons physiology, SOXB1 Transcription Factors physiology, Tumor Suppressor Proteins physiology
- Abstract
Neural stem/progenitor cells maintain their identity via continuous self-renewal and suppression of differentiation. Gain-of-function experiments in the chick revealed an involvement for Sox1-3 transcription factors in the maintenance of the undifferentiated neural progenitor (NP) identity. However, the mechanism(s) employed by each factor has not been resolved. Here, we derived cortical neural/stem progenitor cells from wild-type and Sox1-null mouse embryos and found that Sox1 plays a key role in the suppression of neurogenic cell divisions. Loss of Sox1 leads to progressive depletion of self-renewing cells, elongation of the cell cycle of proliferating cells, and significant increase in the number of cells exiting the cell cycle. In proliferating NP cells, Sox1 acts via a prospero-related homeobox 1 (Prox1)-mediated pathway to block cell cycle exit that leads to neuronal differentiation in vivo and in vitro. Thus, our results demonstrate that Sox1 regulates the size of the cortical NP pool via suppression of Prox1-mediated neurogenic cell divisions., (Copyright © 2010 AlphaMed Press.)
- Published
- 2011
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9. Foxj1 regulates floor plate cilia architecture and modifies the response of cells to sonic hedgehog signalling.
- Author
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Cruz C, Ribes V, Kutejova E, Cayuso J, Lawson V, Norris D, Stevens J, Davey M, Blight K, Bangs F, Mynett A, Hirst E, Chung R, Balaskas N, Brody SL, Marti E, and Briscoe J
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- Animals, Cells, Cultured, Chick Embryo, Chickens, Cilia ultrastructure, Flow Cytometry, Forkhead Transcription Factors genetics, Gene Expression Profiling, Hedgehog Proteins genetics, Homeobox Protein Nkx-2.2, Homeodomain Proteins genetics, Homeodomain Proteins metabolism, Immunohistochemistry, In Situ Hybridization, Mice, Microscopy, Electron, Scanning, Microscopy, Electron, Transmission, NIH 3T3 Cells, Neural Tube ultrastructure, Transcription Factors genetics, Transcription Factors metabolism, Zebrafish Proteins, Cilia metabolism, Forkhead Transcription Factors metabolism, Hedgehog Proteins metabolism, Neural Tube embryology, Neural Tube metabolism, Signal Transduction
- Abstract
Sonic hedgehog signalling is essential for the embryonic development of many tissues including the central nervous system, where it controls the pattern of cellular differentiation. A genome-wide screen of neural progenitor cells to evaluate the Shh signalling-regulated transcriptome identified the forkhead transcription factor Foxj1. In both chick and mouse Foxj1 is expressed in the ventral midline of the neural tube in cells that make up the floor plate. Consistent with the role of Foxj1 in the formation of long motile cilia, floor plate cells produce cilia that are longer than the primary cilia found elsewhere in the neural tube, and forced expression of Foxj1 in neuroepithelial cells is sufficient to increase cilia length. In addition, the expression of Foxj1 in the neural tube and in an Shh-responsive cell line attenuates intracellular signalling by decreasing the activity of Gli proteins, the transcriptional mediators of Shh signalling. We show that this function of Foxj1 depends on cilia. Nevertheless, floor plate identity and ciliogenesis are unaffected in mouse embryos lacking Foxj1 and we provide evidence that additional transcription factors expressed in the floor plate share overlapping functions with Foxj1. Together, these findings identify a novel mechanism that modifies the cellular response to Shh signalling and reveal morphological and functional features of the amniote floor plate that distinguish these cells from the rest of the neuroepithelium.
- Published
- 2010
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10. Distinct Sonic Hedgehog signaling dynamics specify floor plate and ventral neuronal progenitors in the vertebrate neural tube.
- Author
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Ribes V, Balaskas N, Sasai N, Cruz C, Dessaud E, Cayuso J, Tozer S, Yang LL, Novitch B, Marti E, and Briscoe J
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- Animals, Biomarkers metabolism, Chick Embryo, Down-Regulation, Embryo, Mammalian, Embryo, Nonmammalian, Female, Mice, Neurons cytology, Somites growth & development, Time Factors, Zebrafish, Body Patterning physiology, Hedgehog Proteins metabolism, Neural Tube cytology, Neural Tube growth & development, Signal Transduction, Stem Cells physiology
- Abstract
The secreted ligand Sonic Hedgehog (Shh) organizes the pattern of cellular differentiation in the ventral neural tube. For the five neuronal subtypes, increasing levels and durations of Shh signaling direct progenitors to progressively more ventral identities. Here we demonstrate that this mode of action is not applicable to the generation of the most ventral cell type, the nonneuronal floor plate (FP). In chick and mouse embryos, FP specification involves a biphasic response to Shh signaling that controls the dynamic expression of key transcription factors. During gastrulation and early somitogenesis, FP induction depends on high levels of Shh signaling. Subsequently, however, prospective FP cells become refractory to Shh signaling, and this is a prerequisite for the elaboration of their identity. This prompts a revision to the model of graded Shh signaling in the neural tube, and provides insight into how the dynamics of morphogen signaling are deployed to extend the patterning capacity of a single ligand. In addition, we provide evidence supporting a common scheme for FP specification by Shh signaling that reconciles mechanisms of FP development in teleosts and amniotes.
- Published
- 2010
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11. Dynamic assignment and maintenance of positional identity in the ventral neural tube by the morphogen sonic hedgehog.
- Author
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Dessaud E, Ribes V, Balaskas N, Yang LL, Pierani A, Kicheva A, Novitch BG, Briscoe J, and Sasai N
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- Animals, Hedgehog Proteins metabolism, Signal Transduction, Hedgehog Proteins physiology, Neural Tube embryology, Vertebrates embryology
- Abstract
Morphogens are secreted signalling molecules that act in a graded manner to control the pattern of cellular differentiation in developing tissues. An example is Sonic hedgehog (Shh), which acts in several developing vertebrate tissues, including the central nervous system, to provide positional information during embryonic patterning. Here we address how Shh signalling assigns the positional identities of distinct neuronal subtype progenitors throughout the ventral neural tube. Assays of intracellular signal transduction and gene expression indicate that the duration as well as level of signalling is critical for morphogen interpretation. Progenitors of the ventral neuronal subtypes are established sequentially, with progressively more ventral identities requiring correspondingly higher levels and longer periods of Shh signalling. Moreover, cells remain sensitive to changes in Shh signalling for an extended time, reverting to antecedent identities if signalling levels fall below a threshold. Thus, the duration of signalling is important not only for the assignment but also for the refinement and maintenance of positional identity. Together the data suggest a dynamic model for ventral neural tube patterning in which positional information corresponds to the time integral of Shh signalling. This suggests an alternative to conventional models of morphogen action that rely solely on the level of signalling., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2010
- Full Text
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12. Foxa1 and Foxa2 function both upstream of and cooperatively with Lmx1a and Lmx1b in a feedforward loop promoting mesodiencephalic dopaminergic neuron development.
- Author
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Lin W, Metzakopian E, Mavromatakis YE, Gao N, Balaskas N, Sasaki H, Briscoe J, Whitsett JA, Goulding M, Kaestner KH, and Ang SL
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- Animals, Brain metabolism, Cell Differentiation, Cell Lineage, Chromatin Immunoprecipitation, Hepatocyte Nuclear Factor 3-alpha metabolism, Hepatocyte Nuclear Factor 3-beta metabolism, Homeobox Protein Nkx-2.2, LIM-Homeodomain Proteins, Mice, Mice, Inbred C57BL, Stem Cells cytology, Zebrafish Proteins, Brain embryology, Dopamine metabolism, Gene Expression Regulation, Developmental, Hepatocyte Nuclear Factor 3-alpha physiology, Hepatocyte Nuclear Factor 3-beta physiology, Homeodomain Proteins metabolism, Neurons metabolism, Transcription Factors metabolism
- Abstract
Mesodiencephalic dopaminergic neurons control voluntary movement and reward based behaviours. Their dysfunction can lead to neurological disorders, including Parkinson's disease. These neurons are thought to arise from progenitors in the floor plate of the caudal diencephalon and midbrain. Members of the Foxa family of forkhead/winged helix transcription factor, Foxa1 and Foxa2, have previously been shown to regulate neuronal specification and differentiation of mesodiencephalic progenitors. However, Foxa1 and Foxa2 are also expressed earlier during regional specification of the rostral brain. In this paper, we have examined the early function of Foxa1 and Foxa2 using conditional mutant mice. Our studies show that Foxa1 and Foxa2 positively regulate Lmx1a and Lmx1b expression and inhibit Nkx2.2 expression in mesodiencephalic dopaminergic progenitors. Subsequently, Foxa1 and Foxa2 function cooperatively with Lmx1a and Lmx1b to regulate differentiation of mesodiencephalic dopaminergic neurons. Chromatin immunoprecipitation experiments indicate that Nkx2.2 and TH genes are likely direct targets of Foxa1 and Foxa2 in mesodiencephalic dopaminergic cells in vivo. Foxa1 and Foxa2 also inhibit GABAergic neuron differentiation by repressing the Helt gene in the ventral midbrain. Our data therefore provide new insights into the specification and differentiation of mesodiencephalic dopaminergic neurons and identifies Foxa1 and Foxa2 as essential regulators in these processes.
- Published
- 2009
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13. Histopathological lesions in lead intoxicated dogs.
- Author
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Papaioannou N, Vlemmas I, Balaskas N, and Tsangaris T
- Subjects
- Animals, Cerebellum drug effects, Cerebellum ultrastructure, Dog Diseases chemically induced, Dogs, Kidney drug effects, Kidney ultrastructure, Lead Poisoning etiology, Lead Poisoning pathology, Liver drug effects, Liver ultrastructure, Male, Peritoneum drug effects, Peritoneum ultrastructure, Retina drug effects, Retina ultrastructure, Tissue Distribution, Dog Diseases pathology, Lead Poisoning veterinary, Organometallic Compounds toxicity
- Abstract
The ultra-structural lesions of lead poisoning and the deposition of lead in liver, kidney, peritoneum, cerebellum and retina of dogs were studied. Specimens were obtained from 5 3-4 mo-old crossbreed dogs each injected i.p. with a total dose of 120 mg lead acetate, divided in 10 equal doses of 12 mg, administered every other day. Two dogs were controls. Histopathological examination revealed degeneration of the epithelial cells of the urinary tubules, the endothelial cells of the renal capillaries and the hepatocytes. Characteristic lead inclusion bodies were observed intracytoplasmically and intranuclearly in mesothelial and giant cells of the peritoneum. Lead needle-like inclusions were intracytoplasmically in the interstitial connective tissue cells of the kidney, and substantial quantities of lead were in collagen fibers of the interstitial kidney tissue.
- Published
- 1998
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