Lysosomal Storage Disease Caused by Sida carpinifolia Poisoning in Goats

A neurologic disease characterized by ataxia, hypermetria, hyperesthesia, and muscle tremors of the head and neck was observed for 2 years in a flock of 28 Anglo-Nubian and Saanen goats on a farm with 5 ha of pasture. Six newborns died during the first week of life, and five abortions were recorded. The predominant plant in the pasture was Sida carpinifolia. The disease was reproduced experimentally in two goats by administration of this plant. Three goats with spontaneous disease and the two experimental animals were euthanatized and necropsied. No significant gross lesions were observed. Fragments of several organs, including the central nervous system, were processed for histopathology. Small fragments of the cerebellar cortex, liver, and pancreas of two spontaneously poisoned goats and two experimentally poisoned goats were processed for electron microscopy. Multiple cytoplasm vacuoles in hepatocytes, acinar pancreatic cells, and neurons, especially Purkinje cells, were the most striking microscopic lesions in the five animals. Ultrastructural changes included membrane-bound vacuoles in hepatocytes, Kupffer cells, acinar pancreatic cells, Purkinje cells, and the small neurons of the granular cell layer of the cerebellum. Paraffin-embedded sections of the cerebellum and pancreas were submitted for lectin histochemical analysis. The vacuoles in different cerebellar and acinar pancreatic cells reacted strongly to the following lectins: Concanavalia ensiformis, Triticum vulgaris, and succinylated Triticum vulgaris. The pattern of staining, analyzed in Purkinje cells and acinar pancreatic cells coincides with results reported for both swainsonine toxicosis and inherited mannosidosis.

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Spontaneous poisoning by Sida carpinifolia (Malvaceae) in horses

Pesquisa Veterinária Brasileira ◽

10.1590/s0100-736x2017000900005 ◽

2017 ◽

Vol 37 (9) ◽

pp. 926-930 ◽

Cited By ~ 2

Author(s):

Daniele M. Bassuino ◽

Guilherme Konradt ◽

Matheus V. Bianchi ◽

Matheus O. Reis ◽

Saulo P. Pavarini ◽

...

Keyword(s):

Neurodegenerative Disorder ◽

Neurological Diseases ◽

Clinical Signs ◽

Lectin Histochemistry ◽

Lysosomal Storage ◽

Con A ◽

Indolizidine Alkaloids ◽

The Central Nervous System ◽

Progressive Weight Loss ◽

Gross Lesions

ABSTRACT: Sida carpinifolia poisoning causes a chronic neurodegenerative disorder associated with lysosomal storage by indolizidine alkaloids (swainsonine). The epidemiological, clinical, pathological and lectin histochemistry findings of an outbreak of natural poisoning by S. carpinifolia in horses in Rio Grande do Sul state, Brazil, are described. Five horses from a total of 15 that were kept on native pasture with large amounts of S. carpinifolia presented during 90 days clinical signs of progressive weight loss, incoordination, stiff gait and ramble, in addition to exacerbated reactions and locomotion difficulty after induced movement. Four horses died, and one of them was submitted for necropsy. At necropsy, no significant gross lesions were observed. Histological findings observed in the central nervous system were characterized by swollen neurons with cytoplasm containing multiple microvacuoles; these abnormalities were more severe in the thalamus, hippocampus, cerebellum and pons. Using lectin histochemistry, the pons and hippocampus sections stained positive for commercial lectin Con-A, sWGA and WGA. This study aimed to detail S. carpinifolia poisoning in horses to be included in the differential diagnoses of neurological diseases of horses.

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Mannosidosis in Galloway Calves

Veterinary Pathology ◽

10.1177/030098588502200607 ◽

1985 ◽

Vol 22 (6) ◽

pp. 548-551 ◽

Cited By ~ 21

Author(s):

D. H. Embury ◽

I. V. Jerrett

Keyword(s):

Lysosomal Enzyme ◽

Lysosomal Enzymes ◽

Lysosomal Storage ◽

Normal Tissues ◽

Liver And Kidney ◽

The Central Nervous System ◽

Gross Lesions ◽

Renal Tubular ◽

Histologic Changes ◽

The Brain

Mannosidosis was diagnosed in four stillborn Galloway calves and an autolyzed full-term fetus from experimental matings of carrier animals. Gross lesions were moderate internal hydrocephalus, and pallor and enlargement of the liver and kidneys and arthrogryposis. Histologic changes in the central nervous system of each calf were marked foamy vacuolation of the cytoplasm of neurones in the cerebral cortex, thalamus and brainstem, and vacuolation of the Purkinje cells of the cerebellum. Spheroids were common throughout the brain and there was also consistent severe foamy cytoplasmic vacuolation of renal tubular epithelial cells and hepatocytes. The activities of α-mannosidase, the lysosomal enzyme whose activity is deficient in mannosidosis, and activities of five other lysosomal enzymes were compared in brain, liver, and kidney tissues of three mannosidosis-affected calves and normal calf tissues. Tissues from the affected calves had a marked deficiency of α-mannosidase activity compared with the normal tissues; the greatest deficiency was in the liver (99%) and brain (98%). Activities of the other lysosomal enzymes were elevated in the affected tissues compared with normal. Mannosidosis is a lysosomal storage disease that results from a defect in glycoprotein metabolism and affects man,18 Angus and Angus-related breeds of cattle, such as Murray greys,12,21 and the cat.4 The congenital disease is caused by an inherited deficiency of the lysosomal enzyme α-mannosidase,14 and is inherited in an autosomal recessive manner. Mannosidosis was recently reported in a number of aborted and stillborn Australian Galloway calves3 from an experimental breeding trial. This is more detailed account of the histological and biochemical results obtained during the trial.

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New Advanced Strategies for the Treatment of Lysosomal Diseases Affecting the Central Nervous System

Current Pharmaceutical Design ◽

10.2174/1381612825666190708213159 ◽

2019 ◽

Vol 25 (17) ◽

pp. 1933-1950 ◽

Cited By ~ 3

Author(s):

Maria R. Gigliobianco ◽

Piera Di Martino ◽

Siyuan Deng ◽

Cristina Casadidio ◽

Roberta Censi

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Polymeric Nanoparticles ◽

Genetic Diseases ◽

Point Of View ◽

Lysosomal Storage ◽

Enzyme Replacement ◽

Lysosomal Diseases ◽

The Central Nervous System ◽

Enzyme Delivery

Lysosomal Storage Disorders (LSDs), also known as lysosomal diseases (LDs) are a group of serious genetic diseases characterized by not only the accumulation of non-catabolized compounds in the lysosomes due to the deficiency of specific enzymes which usually eliminate these compounds, but also by trafficking, calcium changes and acidification. LDs mainly affect the central nervous system (CNS), which is difficult to reach for drugs and biological molecules due to the presence of the blood-brain barrier (BBB). While some therapies have proven highly effective in treating peripheral disorders in LD patients, they fail to overcome the BBB. Researchers have developed many strategies to circumvent this problem, for example, by creating carriers for enzyme delivery, which improve the enzyme’s half-life and the overexpression of receptors and transporters in the luminal or abluminal membranes of the BBB. This review aims to successfully examine the strategies developed during the last decade for the treatment of LDs, which mainly affect the CNS. Among the LD treatments, enzyme-replacement therapy (ERT) and gene therapy have proven effective, while nanoparticle, fusion protein, and small molecule-based therapies seem to offer considerable promise to treat the CNS pathology. This work also analyzed the challenges of the study to design new drug delivery systems for the effective treatment of LDs. Polymeric nanoparticles and liposomes are explored from their technological point of view and for the most relevant preclinical studies showing that they are excellent choices to protect active molecules and transport them through the BBB to target specific brain substrates for the treatment of LDs.

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The Golgi Material of the Neurones of the Central Nervous System of Sheep Infected with Louping-Ill

Journal of Cell Science ◽

10.1242/jcs.s3-88.1.55 ◽

1947 ◽

Vol s3-88 (1) ◽

pp. 55-63

Author(s):

R. A. R. GRESSON ◽

I. ZLOTNIK

Keyword(s):

Spinal Cord ◽

Central Nervous System ◽

Nervous System ◽

Purkinje Cells ◽

Medulla Oblongata ◽

Motor Nerve ◽

Pyramidal Cells ◽

Cell Processes ◽

The Central Nervous System ◽

Louping Ill

1. The Golgi material of the pyramidal cells of the cerebral cortex, the Purkinje cells of the cerebellum, and the multipolar cells of the medulla oblongata and ventral horns of the spinal cord of the sheep is present as filaments and as irregularly shaped bodies. In some of the cells, particularly in the lamb (Sheep V), the Golgi material has the appearance of a network. As it is frequently present as separate bodies it is suggested that it may always consist of discrete Golgi elements which are sometimes situated in close proximity or in contact with one another. Filamentous Golgi elements are present in the basal part of the cell processes. 2. An examination of neurones from the corresponding regions of the central nervous system of sheep infected experimentally with louping-ill showed that the Golgi material undergoes changes consequent upon the invasion of the cells by the virus. The Golgi material undergoes hypertrophy, and at the same time there is a reduction in the number of filamentous Golgi elements and a reduction in the amount of Golgi substance present in the cell processes. These changes are followed by fragmentation. All the neurones of a particular region are not affected equally at the same time. The Golgi material of the Purkinje cells tends to form groups in the cytoplasm prior to fragmentation. In the multipolar cells of the medulla oblongata the hypertrophy of the Golgi material is not as great as in the other regions of the central nervous system. The Golgi material of the motor nerve-cells of the ventral horns of the spinal cord undergoes considerable hypertrophy which is followed by a grouping of the Golgi elements and fragmentation.

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Colocalization of ghrelin O-acyltransferase and ghrelin in gastric mucosal cells

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.90859.2008 ◽

2009 ◽

Vol 297 (1) ◽

pp. E134-E141 ◽

Cited By ~ 83

Author(s):

Ichiro Sakata ◽

Jing Yang ◽

Charlotte E. Lee ◽

Sherri Osborne-Lawrence ◽

Sherry A. Rovinsky ◽

...

Keyword(s):

Peptide Hormone ◽

Whole Body ◽

Histochemical Analysis ◽

Oxyntic Mucosa ◽

Body Distribution ◽

Naturally Occurring ◽

Mucosal Cells ◽

Membrane Bound ◽

High Degree ◽

Dual Label

Ghrelin is a peptide hormone with many known functions, including orexigenic, blood glucose-regulatory, and antidepressant actions, among others. Mature ghrelin is unique in that it is the only known naturally occurring peptide to be posttranslationally modified by O-acylation with octanoate. This acylation is required for many of ghrelin's actions, including its effects on promoting increases in food intake and body weight. GOAT (ghrelin O-acyltransferase), one of 16 members of the MBOAT family of membrane-bound O-acyltransferases, has recently been identified as the enzyme responsible for catalyzing the addition of the octanoyl group to ghrelin. Although the initial reports of GOAT have localized its encoding mRNA to tissues known to contain ghrelin, it is as yet unclear whether the octanoylation occurs within ghrelin-producing cells or in neighboring cells. Here, we have performed dual-label histochemical analysis on mouse stomach sections and quantitative PCR on mRNAs from highly enriched pools of mouse gastric ghrelin cells to demonstrate a high degree of GOAT mRNA expression within ghrelin-producing cells of the gastric oxyntic mucosa. We also demonstrate that GOAT is the only member of the MBOAT family whose expression is highly enriched within gastric ghrelin cells and whose whole body distribution mirrors that of ghrelin.

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Pathology of Angiostrongylus cantonensis infection in two model avian hosts

Parasitology ◽

10.1017/s0031182020001869 ◽

2020 ◽

pp. 1-4

Author(s):

Barbora Fecková ◽

Priyanka Djoehana ◽

Barbora Putnová ◽

Michaela Valašťanová ◽

Michaela Petríková ◽

...

Keyword(s):

Low Dose ◽

Natural Infection ◽

Clinical Signs ◽

French Polynesia ◽

Angiostrongylus Cantonensis ◽

High Dose ◽

Wide Range ◽

The Central Nervous System ◽

Gross Lesions ◽

Natural Pest Control

Abstract Angiostrongylus cantonensis causes severe neurological disorders in a wide range of warm-blooded animals, including several avian species. A laboratory isolate of A. cantonensis originating from French Polynesia, genotyped as clade 2, was used to assess the effect of experimental infection in chicken and Japanese quail. Low dose groups of birds were infected orally by 100 L3 larvae, high dose groups by 1500 L3 larvae and the birds in the third group were fed three infected snails, mimicking a natural infection. Clinical signs during the first week after infection, haematology, biochemistry, gross lesions and histology findings were used to assess the pathology of the infection. Some of the infected birds showed peripheral eosinophilia, while mild neurological signs were seen in others. No larvae were observed in serial sections of the central nervous system of infected birds 1 week after infection and no major gross lesions were observed during necropsy; histopathology did not reveal lesions directly attributable to A. cantonensis infection. Our results suggest that galliform birds are not highly susceptible to A. cantonensis infection and open a question of the importance of Galliformes in endemic areas as natural pest control, lowering the number of hosts carrying the infective larvae.

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Lysosomal Storage Disorders

10.1093/med/9780197512166.003.0121 ◽

2021 ◽

pp. 1106-1113

Author(s):

Radhika Dhamija ◽

Erin Conboy ◽

Lily C. Wong-Kisiel

Keyword(s):

Lysosomal Storage Diseases ◽

Lysosomal Storage Disorders ◽

Lysosomal Storage ◽

Storage Diseases ◽

Activator Proteins ◽

Autophagic Vacuoles ◽

Enzyme Substrate ◽

Membrane Bound ◽

Considerable Morbidity ◽

Storage Disorders

Lysosomes are membrane-bound organelles that degrade various macromolecules. Lysosomal storage diseases are a clinically, enzymatically, and genetically heterogeneous group of disorders resulting from intracellular accumulation of substrates. Mechanisms of lysosomal storage disorders include 1) primary deficiency of specific hydrolases; 2) defects in activator proteins required for enzyme-substrate interactions in posttranslational modification of enzymes or in transport of the substrate from lysosomes; and 3) abnormalities of fusion between autophagic vacuoles and lysosomes. Substrate accumulation is slowly progressive, leading to considerable morbidity and mortality.

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Infection With a Novel Rickettsiella Species in Emperor Scorpions (Pandinus imperator)

Veterinary Pathology ◽

10.1177/0300985820951495 ◽

2020 ◽

Vol 57 (6) ◽

pp. 858-870

Author(s):

Sushan Han ◽

Aníbal G. Armién ◽

Janet E. Hill ◽

Champika Fernando ◽

Dan S. Bradway ◽

...

Keyword(s):

Electron Microscopy ◽

Transmission Electron Microscopy ◽

Rapid Progression ◽

Protein Coding ◽

Hematopoietic Organ ◽

Transmission Electron ◽

History Of ◽

Gross Lesions ◽

Membrane Bound ◽

Methenamine Silver

Rickettsiella infection was diagnosed in 4 adult emperor scorpions ( Pandinus imperator) from 2 different collections over a 3-year period. One case had a 2-day history of weakness, failure to lift the tail, or respond to stimulation, with rapid progression to death. The other 3 cases were found dead. There were no gross lesions, but histologically the hemolymphatic vasculature and sinuses, presumed hematopoietic organ, heart, midgut and midgut diverticula, nerves, and skeletal muscle were infiltrated with phagocytic and granular hemocytes with necrosis. Phagocytic hemocytes contained abundant intracellular microorganisms that were Fite’s acid-fast-positive, Macchiavello-positive, variably gram-positive or gram-negative, and Grocott’s methenamine silver-negative. By transmission electron microscopy, hemocytes contained numerous phagocytic vacuoles with small dense bacterial forms (mean 0.603 × 0.163 μm) interspersed with large bacterial forms (mean 1.265 × 0.505 μm) and few intermediary forms with electron-dense nucleoids and membrane-bound crystalline arrays (average 4.72 μm). Transmission electron microscopy findings were consistent with bacteria of the family Coxiellaceae. Based on sequencing the 16S ribosomal RNA gene, the identity was confirmed as Rickettsiella, and phylogenetic analysis of protein-coding genes gidA, rspA, and sucB genes suggested the emperor scorpion pathogen as a new species. This study identifies a novel Rickettsiella causing infection in emperor scorpions and characterizes the unique pathological findings of this disease. We suggest this organism be provisionally named Rickettsiella scorpionisepticum.

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Myocardial and Pancreatic Lesions Induced by T-2 Toxin, a Trichothecene Mycotoxin, in Swine

Veterinary Pathology ◽

10.1177/030098588602300312 ◽

1986 ◽

Vol 23 (3) ◽

pp. 310-319 ◽

Cited By ~ 22

Author(s):

V. F. Pang ◽

J. H. Adams ◽

V. R. Beasley ◽

W. B. Buck ◽

W. M. Haschek

Keyword(s):

Light And Electron Microscopy ◽

Ultrastructural Changes ◽

Zymogen Granules ◽

Mononuclear Cell Infiltration ◽

Trichothecene Mycotoxin ◽

Nuclear Pyknosis ◽

Target Organs ◽

Gross Lesions ◽

Sublethal Doses ◽

Histologic Changes

Myocardial and pancreatic lesions induced by sublethal doses of T-2 toxin in swine were characterized by light and electron microscopy. Toxin was given intravenously to six 17- to 18-week-old pigs. Pigs were killed 24 or 48 hours after treatment. Grossly, subendocardial hemorrhages, multifocal pinpoint white foci in myocardium, and pancreatic edema occurred in one treated pig. Histologic changes in myocardium of treated pigs consisted of multifocal edema, mononuclear cell infiltration, myofiber hyalinization, vacuolation, and contraction bands with nuclear pyknosis. Ultrastructurally, there were areas of edema, myofibrillar disorganization, dilation of sarcoplasmic reticulum, and formation of hypercontraction bands. Myocardial mineralization was seen in the pig with gross lesions. Pancreatic changes in treated pigs consisted of multifocal acinar degeneration and necrosis. Ultrastructural changes included irregular dilation of rough endoplasmic reticulum and abnormal zymogen granules. Thus, in addition to radiomimetic lesions of the gastrointestinal tract and lymphoid organs, heart and pancreas are target organs of T-2 toxin in swine.

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Acute Administration of Desformylflustrabromine Relieves Chemically Induced Pain in CD-1 Mice

Molecules ◽

10.3390/molecules24050944 ◽

2019 ◽

Vol 24 (5) ◽

pp. 944 ◽

Cited By ~ 4

Author(s):

Loni Weggel ◽

Anshul Pandya

Keyword(s):

Nicotinic Acetylcholine Receptors ◽

Acetylcholine Receptors ◽

Acute Administration ◽

Allosteric Modulators ◽

Neuronal Nicotinic Acetylcholine Receptors ◽

Nicotinic Acetylcholine ◽

Chemically Induced ◽

The Central Nervous System ◽

Membrane Bound ◽

Pain Test

Neuronal nicotinic acetylcholine receptors are cell membrane-bound ion channels that are widely distributed in the central nervous system. The α4β2 subtype of neuronal nicotinic acetylcholine receptor plays an important role in modulating the signaling pathways for pain. Previous studies have shown that agonists, partial agonists, and positive allosteric modulators for the α4β2 receptors are effective in relieving pain. Desformylflustrabromine is a compound that acts as an allosteric modulator of α4β2 receptors. The aim of this study was to assess the effects of desformylflustrabromine on chemically induced pain. For this purpose, the formalin-induced pain test and the acetic acid-induced writhing response test were carried out in CD-1 mice. Both tests represent chemical assays for nociception. The results show that desformylflustrabromine is effective in producing an analgesic effect in both tests used for assessing nociception. These results suggest that desformylflustrabromine has the potential to become a clinically used drug for pain relief.

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