scholarly journals Effect of experimental folate deficiency on lipid metabolism in liver and brain

1982 ◽  
Vol 47 (3) ◽  
pp. 505-520 ◽  
Author(s):  
B. Åkesson ◽  
C. Fehling ◽  
M. Jägerstad ◽  
U. Stenram
Keyword(s):  
Morphological Changes ◽  
Fatty Infiltration ◽  
Light And Electron Microscopy ◽  
Intraperitoneal Administration ◽  
Folate Deficiency ◽  
Neurological Dysfunction ◽  
Liver Phospholipid ◽  
Deficient Diet ◽  
Low Concentrations ◽  
Parenchymal Cells

1. Rats were given a purified folate-deficient diet containing 5 g succinylsulphathiazole/kg for 4–5 months in two experiments. Control rats were supplemented with folic acid in the drinking-water.2. Weight gain was much below normal in the folate-deprived rats after the first month. Very low folate levels were recorded in blood, liver and peripheral nerve (12–33% of control). In Ihe central nervous system, including the cerebrospinal fluid, the folate depletion was less conspicuous (50–80% of control). Only marginal signs of anaemia were found and no signs of neurological dysfunction were detected, using nerve conduction velocity measurement and co-ordination tests.3. Light and electron microscopy of the folate deficient liver revealed fatty infiltration, and enlargement of liver parenchymal cells, nuclei and nucleoli. There was often a considerable amount of bile ductular cells in the lobuli but no cirrhosis. The morphological changes resembled those observed in choline deficiency.4. Phospholipid N-methylation in liver was depressed in folate deficiency. This was probably due to a decreased availability of S-adenosylmethionine caused by the low concentrations of methylated folate in liver. Intraperitoneal administration of methionine did not normalize phospholipid methylation.5. In folate deficiency the proportion of ethanolamine phosphoglyceride in liver was increased at the expense of choline phosphoglyceride, which is consistent with a decreased phospholipid methylation. Also an increase in liver triacylglycerol was noted, in accordance with the morphological observations. Brain lipid composition was unchanged.6. After the injection of labelled ethanolamine, isotope accumulated in liver phosphoethanolamine in folate deficiency, probably due to an impairment of the CTP: ethanolaminephosphate cytidylyltransferase(EC2.7.7.14) reaction. The mechanism of this impairment is discussed.7. Although the low concentrations of folate was the main nutritional change in the deprived animals, changes with respect to vitamin B12and maybe also choline cannot be excluded. We conclude that some of the changes in folate deficiency, i.e. fatty liver and decreased biosynthesis of liver phospholipids may be due to a precipitated deficiency of lipotropic agents, whereas other differences may be specific for deficiency of folateper se, such as changes in liver phospholipid fatty acids and some of the morphological aberrations.

scholarly journals Inhibition of NAD+-dependent histone deacetylases (sirtuins) causes growth arrest and activates both apoptosis and autophagy in the pathogenic protozoan Trypanosoma cruzi

Parasitology ◽  
2014 ◽  
Vol 141 (6) ◽  
pp. 814-825 ◽  
Author(s):  
PHERCYLES VEIGA-SANTOS ◽  
LISSA CATHERINE REIGNAULT ◽  
KILIAN HUBER ◽  
FRANZ BRACHER ◽  
WANDERLEY DE SOUZA ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Histone Deacetylases ◽  
Morphological Changes ◽  
Light And Electron Microscopy ◽  
Chronic Phase ◽  
Physiological Processes ◽  
Low Concentrations ◽  
Disease Therapy ◽  
New Compounds

SUMMARYChagas disease, which is caused by the parasite Trypanosoma cruzi, affects approximately 7–8 million people in Latin America. The drugs available to treat this disease are ineffective against chronic phase disease and are associated with toxic side effects. Therefore, the development of new compounds that can kill T. cruzi at low concentrations is critically important. Herein, we report the effects of a novel 3-arylideneindolin-2-one that inhibits sirtuins, which are highly conserved proteins that are involved in a variety of physiological processes. The compound KH-TFMDI was tested against the epimastigote, trypomastigote and amastigote forms of T. cruzi, and its effects were evaluated using flow cytometry, light and electron microscopy. KH-TFMDI inhibited the replication of T. cruzi intracellular amastigotes with an IC50 of 0·5±0·2 μm, which is significantly lower than the IC50 of benznidazole. The compound also lysed the highly infectious bloodstream trypomastigotes (BST) with LC50 values of 0·8±0·3 μm at 4 °C and 2·5±1·1 μm at 37 °C. KH-TFMDI inhibited cytokinesis and induced several morphological changes in the parasite, leading to its death by apoptosis and autophagy. This study highlights sirtuins as a potential new target for Chagas disease therapy.

The Effect of Vitamin A on the Intermittent Nitrogen Dioxide Gas Exposure in Hamsters

1976 ◽  
Vol 34 ◽  
pp. 176-177
Author(s):  
J.C.S. Kim ◽  
M.G. Jourden ◽  
E.S. Carlisle
Keyword(s):  
Electron Microscopy ◽  
Vitamin A ◽  
Nitrogen Dioxide ◽  
Chronic Exposure ◽  
Light And Electron Microscopy ◽  
Specific Effect ◽  
Deficient Diet ◽  
Intermittent Exposure ◽  
Hypovitaminosis A ◽  
Gas Exposure

Chronic exposure to nitrogen dioxide in rodents has shown that injury reaches a maximum after 24 hours, and a reparative adaptive phase follows (1). Damage occurring in the terminal bronchioles and proximal portions of the alveolar ducts in rats has been extensively studied by both light and electron microscopy (1).The present study was undertaken to compare the response of lung tissue to intermittent exposure to 10 ppm of nitrogen dioxide gas for 4 hours per week, while the hamsters were on a vitamin A deficient diet. Ultrastructural observations made from lung tissues obtained from non-gas exposed, hypovitaminosis A animals and gas exposed animals fed a regular commercially prepared diet have been compared to elucidate the specific effect of vitamin A on nitrogen dioxide gas exposure. The interaction occurring between vitamin A and nitrogen dioxide gas has not previously been investigated.

Alteration of Mitochondria in Oxythiamine-Induced, Acute Thiamine Deficiency in the Mouse

1976 ◽  
Vol 34 ◽  
pp. 284-285
Author(s):  
Itaru Watanabe ◽  
Dante G. Scarpelli
Keyword(s):  
Electron Microscopy ◽  
Adult Male ◽  
Thiamine Deficiency ◽  
Light And Electron Microscopy ◽  
Fatty Change ◽  
Deficient Diet ◽  
Subcutaneous Injections ◽  
Swiss Mice ◽  
Time Period ◽  
Ad Libitum

Acute thiamine deficiency was produced in mice by the administration of oxythiamine, a thiamine analogue, superimposed upon a thiamine deficient diet. Adult male Swiss mice (30 gm. B.W.) were fed with a thiamine deficient diet ad libitumand were injected with oxythiamine (170 mg/Kg B.W.) subcutaneously on days 4 and 10. On day 11, severe lassitude and anorexia developed, followed by death within 48 hours. The animals treated daily with subcutaneous injections of thiamine (300 μg/Kg B.W.) from day 11 through 15 were kept alive. Similarly, feeding with a diet containing thiamine (600 μg/Kg B.W./day) from day 9 through 17 reversed the condition. During this time period, no fatal illness occurred in the controls which were pair-fed with a thiamine deficient diet.The oxythiamine-treated mice showed a significant enlargement of the liver, which weighed approximately 1.5 times as much as that of the pair-fed controls. By light and electron microscopy, the hepatocytes were markedly swollen due to severe fatty change and swelling of the mitochondria.

REACTIVE CHANGES OF LIVER AND KIDNEY HISTOLOGICAL ELEMENTS IN MURINE MODELS OF SEPSIS CAUSED BY ADMINISTRATION OF DIFFERENT STRAINS TO MICE

2020 ◽  
pp. 66-71
Author(s):  
Татьяна Геннадьевна Боровая ◽  
Владимир Григорьевич Жуховицкий ◽  
Мария Николаевна Черкасова
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Morphological Changes ◽  
Blood Stasis ◽  
Intraperitoneal Administration ◽  
Liver Parenchyma ◽  
Experimental Models ◽  
Control Group ◽  
Reactive Changes ◽  
Liver And Kidney ◽  
Different Strains

Цель - выявление реактивных изменений гистологических элементов печени и почек у мышей в экспериментальных моделях сепсиса, вызванного штаммами 1840 и 1623 Pseudomonas aeruginosa (PsA1840, 1623). Материал и методы. Сепсис моделировали на двух группах половозрелых самцов мышей линии C57Bl/6 интраперитонеальным введением Pseudomonas aeruginosa. Животным 1-й группы (8 особей) вводили штамм 1840, животным 2-й группы (12 особей) - штамм 1623. Контрольная группа состояла из 3 животных. Перед началом опыта штаммы тестировали на присутствие генов экзотоксинов U, S, T, Y (ExoU, ExoS, ExoT, ExoY) с помощью полимеразной цепной реакции (ПЦР). Для визуализации продуктов ПЦР применяли электрофорез в горизонтальном 1,5 % агарозном геле. Животных вскрывали на терминальной стадии сепсиса. Серийные парафиновые срезы печени и почек толщиной 4 мкм окрашивали гематоксилином - эозином, анализировали особенности гистоструктуры органов и фотографировали в световом микроскопе «AxioPlus» (фирма Zeiss, Германия). Результаты. Штамм PsA 1840, имеющий ген exoU, вызывал выраженные деструктивные изменения пластинок гепатоцитов и замещение участков паренхимы печени гомогенным эозинофильным веществом. Присутствовали признаки стаза крови в синусоидных капиллярах, расширение и тромбоз центральных вен, немногочисленные скопления лейкоцитов. Морфологические изменения нефронов состояли в локальных деструктивных изменениях проксимальных канальцев на периферии коркового вещества почек. При введении PsA1623, имеющего ген exoS, возникали массовая гибель почечных телец и дегенерация канальцев нефронов. В печени дольковая гистоархитектура в основном сохранялась. Выводы. Предполагается связь выявленных различий в реактивных изменениях гистологических элементов печени и почек в подопытных группах с особенностями геномов штаммов PsA, использованных для моделирования сепсиса. Objective - to identify reactive changes of liver and kidney histological elements in experimental models of sepsis in mice caused by 1840 and 1623 Pseudomonas aeruginosa strains (PsA1840, 1623). Material and methods. Sepsis was modeled in two groups of mature male C57Bl/6 mice by intraperitoneal administration of Pseudomonas aeruginosa. Strain 1840 was administered to animals of the first group (n=8), animals of the second group (n=12) were administered strain 1623; the control group consisted of 3 animals. Before the experiment, the strains were tested for the presence of genes of exotoxins U, S, T, Y (ExoU, ExoS, ExoT, ExoY) using polymerase chain reaction (PCR). Electrophoresis in horizontal 1,5 % agarose gel was used to visualize PCR products. The animals were euthanized at the terminal stage of sepsis. The extracted liver and kidneys were fixed according to the generally accepted histological method, and embedded into paraffin blocks. Serial 4 μm thick sections of organs were stained with hematoxylin and eosin, analyzed and photographed using «AxioPlus» light microscope (Zeiss, Germany). Results. Strain PsA 1840, carrying the gene of exotoxin U (ExoU), caused severe destructive changes of hepatocytes plates and the replacement of the liver parenchyma with homogeneous eosinophilic substance. There were signs of blood stasis in sinusoidal capillaries, expansion and thrombosis of central veins, a few accumulations of leukocytes. Morphological changes of nephrons consisted of local destructive changes in the proximal tubules at the periphery of kidney cortical substance. After the introduction of PsA1623, carrying the gene of exotoxin S (ExoS), the massive death of renal corpuscles and degeneration of nephron tubules were registered. However, the lobular histoarchitecture in the liver remained mostly unaltered. Conclusions. It is supposed that there is a possible connection of the observed differences in reactive changes of liver and kidney histological elements in two experimental groups with genome features of PsA strains used for the sepsis modeling.

A Method of Maintaining Parenchymal Cells from Adult Rat Liver In Vitro

1972 ◽  
Vol 11 (1) ◽  
pp. 249-260
Author(s):  
J. ALWEN ◽  
JENNIFER J. GALLHAI-ATCHARD
Keyword(s):  
Electron Microscopy ◽  
Endothelial Cells ◽  
Protein Synthesis ◽  
Light And Electron Microscopy ◽  
Rat Hepatocytes ◽  
Adult Rat ◽  
Adult Rat Hepatocytes ◽  
Rna And Protein Synthesis ◽  
Parenchymal Cells

A method for preparing suspensions of adult rat hepatocytes suitable for maintenance in vitro is described. Cultures were established from the cell suspensions by the squash technique. Cells were examined by light and electron microscopy; histochemically for glycogen, bile, lipid and glucose-6-phosphatase; and by autoradiography for DNA, RNA and protein synthesis. Hepatocytes could be maintained in vitro for at least 3 days and began to aggregate after 1 day. Uridine and leucine were incorporated, but not thymidine. Cultures consisted mainly of hepatocytes, though reticulo-endothelial cells were sometimes present.

scholarly journals A histochemical approach to the mechanism of action of cisplatin and its analogues.

1993 ◽  
Vol 41 (7) ◽  
pp. 1053-1073 ◽  
Author(s):  
S K Aggarwal
Keyword(s):  
Membrane Transport ◽  
Mechanism Of Action ◽  
Morphological Changes ◽  
Calcium Supplementation ◽  
Rat Kidney ◽  
Light And Electron Microscopy ◽  
Atp Synthesis ◽  
Chloride Ion ◽  
Tissue Homogenates ◽  
Cancer Agent

The effects of cisplatin (CDDP), a potent anti-cancer agent, and its various analogues were analyzed for any biochemical changes involving Ca2+ and lysosomal and membrane-associated transport enzymes in rat kidney, liver, serum, urine, tissue homogenates, and isolated mitochondria. Correlation was made with any morphological changes observed by light and electron microscopy to gain an insight into the mechanism of action of various platinum coordination complexes. CDDP in its hydrolyzed state under conditions of low chloride ion concentrations causes uncoupling of oxidative phosphorylation, calcium efflux from the mitochondria, inhibits ATP synthesis, lowers membrane-associated calcium and various membrane transport enzymes, and induces an increase in the number of lysosomes. Enzymes such as alkaline phosphatase are stripped from the brush borders of the proximal tubule cells and are discharged in the urine. However, daily IV injections of calcium (1.1 ml of 1.3% CaCl2) supplementation protect the membrane-associated enzymes from cisplatin action. Carboplatin (CBDCA), an analogue of CDDP and the least nephrotoxic of all its analogues, shows little effect on the membrane-associated transport enzymes. Therefore, cisplatin and its various analogues seem to affect the membrane transport enzymes to varying degrees with related nephrotoxicity. Calcium supplementation seems to protect these enzymes and preserve kidney function.

Morphological changes in putrefactive anaerobe 3679 (Clostridium sporogenes) induced by sorbate, hydrochloric acid, and nitrite

1989 ◽  
Vol 35 (3) ◽  
pp. 388-398 ◽  
Author(s):  
Irene E. Ronning ◽  
Hilmer A. Frank
Keyword(s):  
Cell Wall ◽  
Hydrochloric Acid ◽  
Growth Regulation ◽  
Morphological Changes ◽  
Light And Electron Microscopy ◽  
Normal Growth ◽  
Outer Wall ◽  
Exponential Growth Phase ◽  
Clostridium Sporogenes ◽  
Cellular Debris

Putrefactive anaerobe 3679 (Clostridium sporogenes), a gram-positive bacterium, was examined by light and electron microscopy during normal growth and in a medium containing sorbate (50 mM, pH 6.5), hydrochloric acid (pH of medium adjusted from 7 to 5 with HCl), or nitrite (1 mM, pH 7). During the early exponential growth phase, untreated cells were filamentous and nonseptate, but became septate later and divided when the culture entered the stationary phase. Untreated short and filamentous cells had a double-layered cell wall. Sorbate-treated cells were usually filamentous and nonseptate, but with distorted shapes characterized by numerous bends and bulges. Septation, when present, resulted in minicells. The inner cell wall appeared to be thickened and the outer wall was absent in many areas. Acid-treated cells were similar to sorbate-treated cells but contained septa. Considerable cellular debris was present in the suspension. Nitrite-treated cells were also filamentous, bent, and bulged but the cell wall appeared normal. Considerable cellular debris was also present in suspensions of nitrite-treated cells. Changes in morphology are discussed in relation to possible mechanisms of cell growth regulation and the inhibitory action of sorbate, acid, and nitrite.Key words: putrefactive anaerobe 3679, sorbate, hydrochloric acid, nitrite.

THE ROLE OF RIBOFLAVIN IN MONOAMINE OXIDASE ACTIVITY

1963 ◽  
Vol 41 (1) ◽  
pp. 57-64 ◽  
Author(s):  
M. H. Wiseman-Distler ◽  
T. L. Sourkes
Keyword(s):  
Monoamine Oxidase ◽  
De Novo ◽  
Intraperitoneal Administration ◽  
Enzymatic System ◽  
Irreversible Inhibitor ◽  
Riboflavin Deficiency ◽  
Deficient Diet ◽  
Hydroxyindoleacetic Acid

The role of riboflavin in the activity of monoamine oxidase (MAO) was investigated by omitting the vitamin from the diet of rats which were further treated with iproniazid, an irreversible inhibitor of the enzyme. The rate of recovery from the inhibition, presumably reflecting de novo synthesis of the enzyme, was estimated by measuring the excretion of the acidic metabolites formed after intraperitoneal administration of serotonin (5 HT) and dopamine. Consumption of the deficient diet did not impair the action of MAO on these amines. After injection of iproniazid, return to control levels of MAO activity was slower when measured by the oxidation of dopamine than of 5 HT; there was a small but significant effect of riboflavin deficiency upon the conversion of 5 HT to 5-hydroxyindoleacetic acid. This was probably due to enhanced inhibition of MAO observed in deficient rats, an effect that was also obtained when inhibitors other than iproniazid were used in vivo. Similarly, disappearance of 5 HT during incubation with a supernatant prepared from liver of deficient rats was also affected to a greater extent by these inhibitors than when the enzymatic system was prepared from control livers. This finding suggests that riboflavin deficiency renders MAO more susceptible to inhibition.

scholarly journals Enhanced Delivery of 4-Thioureidoiminomethylpyridinium Perchlorate in Tuberculosis Models with IgG Functionalized Poly(Lactic Acid)-Based Particles

Pharmaceutics ◽  
2018 ◽  
Vol 11 (1) ◽  
pp. 2 ◽  
Author(s):  
Leonid Churilov ◽  
Viktor Korzhikov-Vlakh ◽  
Ekaterina Sinitsyna ◽  
Dmitry Polyakov ◽  
Oleg Darashkevich ◽  
...  
Keyword(s):  
Lactic Acid ◽  
Morphological Changes ◽  
Multiple Drug Resistance ◽  
Intraperitoneal Administration ◽  
Oral Drug ◽  
Poly Lactic Acid ◽  
Multiple Drug ◽  
Single Chain ◽  
Inner Organs ◽  
Drug Solution

The compound 4-thioureidoiminomethylpyridinium perchlorate (perchlozone©) is a novel anti-tuberculosis drug that is active in multiple drug resistance cases, but the compound is hepatotoxic. To decrease the systemic load and to achieve targeting, we encapsulated the drug into poly(lactic acid)-based micro- (1100 nm) and nanoparticles (170 nm) that were modified with single-chain camel immunoglobulin G (IgG) for targeting. Both micro- and nanoparticles formed stable suspensions in saline solution at particle concentrations of 10–50 mg/mL. The formulations were injected intraperitoneally and intravenously into the mice with experimental tuberculosis. The survival of control animals was compared to that of mice which were treated with daily oral drug solution, single intraperitoneal administration of drug-loaded particles, and those treated both intravenously and intraperitoneally by drug-loaded particles modified with polyclonal camel IgGs. The distribution of particles in the organs of mice was analyzed with immunofluorescence and liquid chromatography/mass spectrometry. Morphological changes related to tuberculosis and drug toxicity were registered. Phagocytic macrophages internalized particles and transported them to the foci of tuberculosis in inner organs. Nanoparticle-based drug formulations, especially those with IgG, resulted in better survival and lower degree of lung manifestations than the other modes of treatment.

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