scholarly journals STRUCTURAL CHANGES IN ISOLATED LIVER MITOCHONDRIA OF RATS DURING ESSENTIAL FATTY ACID DEFICIENCY

1964 ◽  
Vol 21 (1) ◽  
pp. 15-26 ◽  
Author(s):  
Janet A. Smith ◽  
Hector F. DeLuca
Keyword(s):  
Atpase Activity ◽  
Structural Damage ◽  
Structural Changes ◽  
Essential Fatty Acids ◽  
Saturated Fat ◽  
Respiratory Control ◽  
Liver Mitochondria ◽  
Structural Defects ◽  
Thin Sections ◽  
Fatty Acid Deficiency

Liver mitochondria isolated in 0.44 M sucrose from rats deficient in essential fatty acids (EFA) oxidized citrate, succinate, α-ketoglutarate, glutamate, and pyruvate at a faster rate than did mitochondria isolated from normal rats; however, the oxidation of malate, caprylate, and ß-hydroxybutyrate was not significantly increased. The mitochondria from deficient rats exhibited an increased ATPase activity and extensive structural damage as revealed by electron microscope examination of thin sections. An increase in citrate oxidation and ATPase activity, together with some structural damage, could be demonstrated as early as the 4th week in rats on a fat-free diet. Saturated fat in the diet did not prevent the change in mitochondrial structure but accelerated its appearance. Both the biochemical and structural defects could be reversed within three weeks after feeding deficient rats a source of EFA. In the presence of a phosphate acceptor the effect of EFA deficiency on substrate oxidation was largely eliminated. A trend toward a reduced efficiency of oxidative phosphorylation was noted in mitochondria from EFA-deficient rats, but significant uncoupling was found only in the case of citrate, ß-hydroxybutyrate, and glutamate in the presence of malonate. Together with the increased ATPase activity, the uncoupling of phosphorylation could account for the poor respiratory control found with the deficient preparation. However, EFA deficiency was without effect on the respiration of liver slices, which supports the belief that the observed changes in oxidation and phosphorylation are an artifact resulting from damage sustained by the deficient mitochondria during their isolation.

scholarly journals Increased Tissue Penetration of Doxorubicin in Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) after High-Intensity Ultrasound (HIUS)

2019 ◽  
Vol 2019 ◽  
pp. 1-6 ◽  
Author(s):  
Veria Khosrawipour ◽  
Sören Reinhard ◽  
Alice Martino ◽  
Tanja Khosrawipour ◽  
Mohamed Arafkas ◽  
...  
Keyword(s):  
Intraperitoneal Chemotherapy ◽  
High Intensity ◽  
Structural Damage ◽  
Structural Changes ◽  
Therapeutic Option ◽  
Tissue Penetration ◽  
High Intensity Ultrasound ◽  
Tissue Samples ◽  
Thin Sections ◽  
Peritoneal Tissue

Background. High‐intensity ultrasound (HIUS) has been studied for the past two decades as a new therapeutic option for solid tumor direct treatment and a method for better chemotherapy delivery and perfusion. This treatment approach has not been tested to our knowledge in peritoneal metastatic therapy, where limited tissue penetration of intraperitoneal chemotherapy has been a main problem. Both liquid instillations and pressurized aerosols are affected by this limitation. This study was performed to evaluate whether HIUS improves chemotherapy penetration rates. Methods. High-intensity ultrasound (HIUS) was applied for 0, 5, 30, 60, 120, and 300 seconds on the peritoneal tissue samples from fresh postmortem swine. Samples were then treated with doxorubicin via pressurized intraperitoneal aerosol chemotherapy (PIPAC) under 12 mmHg and 37°C temperature. Tissue penetration of doxorubicin was measured using fluorescence microscopy on frozen thin sections. Results. Macroscopic structural changes, identified by swelling of the superficial layer of the peritoneal surface, were observed after 120 seconds of HIUS. Maximum doxorubicin penetration was significantly higher in peritoneum treated with HIUS for 300 seconds, with a depth of 962.88 ± 161.4 μm (p < 0.05). Samples without HIUS had a penetration depth of 252.25 ± 60.41. Tissue penetration was significantly increased with longer HIUS duration, with up to 3.8-fold increased penetration after 300 sec of HIUS treatment. Conclusion. Our data indicate that HIUS may be used as a method to prepare the peritoneal tissue for intraperitoneal chemotherapy. Higher tissue penetration rates can be achieved without increasing chemotherapy concentrations and preventing structural damage to tissue using short time intervals. More studies need to be performed to analyze the effect of HIUS in combination with intraperitoneal chemotherapy.

VARIATIONS IN LIPID INTAKE AND THEIR INFLUENCE ON RESPIRATION AND TRICARBOXYLIC ACID CYCLE ACTIVITY

1965 ◽  
Vol 43 (9) ◽  
pp. 1575-1587 ◽  
Author(s):  
Hector F. DeLuca
Keyword(s):  
Fatty Acids ◽  
Vitamin D ◽  
Vitamin A ◽  
Tricarboxylic Acid Cycle ◽  
Essential Fatty Acids ◽  
Respiratory Control ◽  
Liver Mitochondria ◽  
Tricarboxylic Acid ◽  
Membrane Systems ◽  
Acid Cycle

The possible role of dietary lipids and lipid-soluble constituents in the tricarboxylic acid cycle, respiratory systems, and mitochondrial structure is discussed, with special emphasis on vitamin D, vitamin A, and essential fatty acids. Deficiency of any of these substances produces structural alterations in isolated kidney or liver mitochondria. In the case of vitamin D deficiency the structural alteration in kidney mitochondria is accompanied by an increased rate of citrate and isocitrate oxidation and a decreased transfer of calcium ions from inside to outside the mitochondria. Vitamin D added in vitro or given to the intact rat specifically decreases citrate oxidation and increases the translocation of calcium. Vitamin A deficiency increases the respiration of liver homogenates and mitochondria in the absence of phosphate acceptor, an effect which could readily be reversed within 48 hours after vitamin A administration. Increased ATPase and decreased respiratory control were also noted in liver mitochondria from vitamin A deficient rats. The structural change as well as the biochemical lesions could also be reversed within 48 hours after vitamin A administration. Similar experiments with essential fatty acid deficient mitochondria also revealed a high ATPase, low respiratory control, and marked structural damage. These changes could be reversed by the feeding of essential fatty acids to the deficient animals for 1–3 weeks. Despite many attempts, it was not possible to demonstrate structural changes in mitochondria in situ as a result of any of the deficiencies described. It is suggested that the respiratory and tricarboxylic acid cycle changes that have been attributed to the lipid constituents of the diet are secondary to alterations in subcellular membrane systems. The use of these membrane systems as tools or models in a study of the mechanism of action of the dietary lipid and lipid-soluble materials is discussed.

scholarly journals Deterioration of rat liver mitochondria under conditions of metabolite deprivation

1980 ◽  
Vol 188 (3) ◽  
pp. 817-822 ◽  
Author(s):  
J W Parce ◽  
P I Spach ◽  
C C Cunningham
Keyword(s):  
Atpase Activity ◽  
Sucrose Solution ◽  
Adenine Nucleotides ◽  
Respiratory Control ◽  
Liver Mitochondria ◽  
Phospholipid Metabolism ◽  
Rat Liver Mitochondria ◽  
Second Phase ◽  
Mitochondrial Atpase ◽  
Sequence Of Events

In a previous study [Parce, Cunningham & Waite (1978) Biochemistry 17, 1634-1639] changes in mitochondrial phospholipid metabolism and energy-linked functions were monitored as coupled mitochondria were aged in iso-osmotic sucrose solution at 18 degrees C. The sequence of events that occur in mitochondrial deterioration under the above conditions have been established more completely. Total adenine nucleotides are depleted early in the aging process, and their loss parallels the decline in respiratory control. Related to the loss of total adenine nucleotides is a dramatic decrease in ADP and ATP translocation (uptake). The decline of respiratory control is due primarily to a decrease in State-3 respiration; loss of this respiratory activity can be related to the decline in ADP translocation. Mitochondrial ATPase activity does not increase significantly until State-4 respiration has increased appreciably. At the time of loss of respiratory control the ATPase activity increases to equal the uncoupler-stimulated activity. The H+/O ratio and P/O ratios do not decrease appreciably until respiratory control is lost. Similarly, permeability of the membrane to the passive diffusion of protons increases only after respiratory control is lost. There observations reinforce our earlier conclusion that there are two main phases in mitochondrial aging. The first phase is characterized by loss of the ability to translocate adenine nucleotides. The second phase is characterized by a decline in the ability of the mitochondrion to conserve energy (i.e. maintain a respiration-driven proton gradient) and to synthesize ATP.

Evaluation of single-electron movies of glutamine synthetase molecules

1983 ◽  
Vol 41 ◽  
pp. 280-281
Author(s):  
W. Kunath ◽  
E. Zeitler ◽  
M. Kessel
Keyword(s):  
Electron Microscope ◽  
Glutamine Synthetase ◽  
Electron Irradiation ◽  
Structural Damage ◽  
Structural Changes ◽  
Single Electron ◽  
Continuous Series ◽  
Digital Recording ◽  
Recording Device ◽  
Low Exposure

The features of digital recording of a continuous series (movie) of singleelectron TV frames are reported. The technique is used to investigate structural changes in negatively stained glutamine synthetase molecules (GS) during electron irradiation and, as an ultimate goal, to look for the molecules' “undamaged” structure, say, after a 1 e/Å2 dose.The TV frame of fig. la shows an image of 5 glutamine synthetase molecules exposed to 1/150 e/Å2. Every single electron is recorded as a unit signal in a 256 ×256 field. The extremely low exposure of a single TV frame as dictated by the single-electron recording device including the electron microscope requires accumulation of 150 TV frames into one frame (fig. lb) thus achieving a reasonable compromise between the conflicting aspects of exposure time per frame of 3 sec. vs. object drift of less than 1 Å, and exposure per frame of 1 e/Å2 vs. rate of structural damage.

scholarly journals Imaging of Joint and Soft Tissue Involvement in Systemic Lupus Erythematosus

2021 ◽  
Vol 23 (9) ◽  
Author(s):  
Andrea Di Matteo ◽  
Gianluca Smerilli ◽  
Edoardo Cipolletta ◽  
Fausto Salaffi ◽  
Rossella De Angelis ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Soft Tissue ◽  
Lupus Erythematosus ◽  
Structural Damage ◽  
Structural Changes ◽  
Soft Tissues ◽  
Imaging Techniques ◽  
Joint Involvement ◽  
Systemic Lupus ◽  
Muscle Involvement

Abstract Purpose of Review To highlight the potential uses and applications of imaging in the assessment of the most common and relevant musculoskeletal (MSK) manifestations in systemic lupus erythematosus (SLE). Recent Findings Ultrasound (US) and magnetic resonance imaging (MRI) are accurate and sensitive in the assessment of inflammation and structural damage at the joint and soft tissue structures in patients with SLE. The US is particularly helpful for the detection of joint and/or tendon inflammation in patients with arthralgia but without clinical synovitis, and for the early identification of bone erosions. MRI plays a key role in the early diagnosis of osteonecrosis and in the assessment of muscle involvement (i.e., myositis and myopathy). Conventional radiography (CR) remains the traditional gold standard for the evaluation of structural damage in patients with joint involvement, and for the study of bone pathology. The diagnostic value of CR is affected by the poor sensitivity in demonstrating early structural changes at joint and soft tissue level. Computed tomography allows a detailed evaluation of bone damage. However, the inability to distinguish different soft tissues and the need for ionizing radiation limit its use to selected clinical circumstances. Nuclear imaging techniques are valuable resources in patients with suspected bone infection (i.e., osteomyelitis), especially when MRI is contraindicated. Finally, dual energy X-ray absorptiometry represents the imaging mainstay for the assessment and monitoring of bone status in patients with or at-risk of osteoporosis. Summary Imaging provides relevant and valuable information in the assessment of MSK involvement in SLE.

scholarly journals EFFECT OF GAMMA IRRADIATION ON THE DESOXYRIBONUCLEASE II ACTIVITY OF ISOLATED MITOCHONDRIA

1957 ◽  
Vol 3 (2) ◽  
pp. 239-248 ◽  
Author(s):  
Shigefumi Okada ◽  
Lee D. Peachey
Keyword(s):  
Structural Damage ◽  
Liver Homogenate ◽  
Liver Mitochondria ◽  
Structural Elements ◽  
Dnase Ii ◽  
Mitochondrial Structure ◽  
Co60 Source ◽  
Mitochondrial Suspension ◽  
High Doses ◽  
Isolated Liver

1. Exposure of isolated liver mitochondria to high doses of gamma rays from a Co60 source causes the level of DNase II activity to increase. Treatment of the mitochondria with sonic vibration causes a further elevation of the activity to a level which is independent of the prior radiation dose. 2. Such increased mitochondrial DNase II activity appears to be due to the "structural damage" of the subcellular particulates caused by the ionizing radiation. Other methods of disrupting the mitochondrial structure also cause increased DNase II activity. A causal relationship between the structural alteration and the increased enzymatic activity is postulated. 3. The DNase II activity appears to be closely associated with the structural elements of the mitochondria and remains associated with the fragments after irradiation. 4. Upon irradiation, the mitochondrial suspension releases ultraviolet-absorbing materials which are probably nucleotide in nature. 5. The possibility of localization of DNase activity in the lysosome fraction of de Duve (15) is discussed. It is felt that DNase II is at least in part a mitochondrial enzyme and that probably the conclusions drawn here would be applicable to any DNase II present in the lysosomes as well. 6. Irradiation of whole liver homogenate causes no increased DNase II activity. The experiments do not provide any information on the presence or action of protective substances in the homogenate.

scholarly journals Structural defects in rat liver deoxyribonucleic acid. Endogenous single-strained regions in comparison with damage induced in vivo by a carcinogen

1979 ◽  
Vol 179 (2) ◽  
pp. 341-352 ◽  
Author(s):  
B W Stewart ◽  
P H Huang ◽  
M J Brian
Keyword(s):  
Rat Liver ◽  
Structural Damage ◽  
Deae Cellulose ◽  
Minor Component ◽  
Structural Defects ◽  
Structural Abnormality ◽  
Denaturation Kinetics ◽  
Limited Digestion ◽  
A Minor

Rat liver DNA may be separated into two fractions by stepwise elution from benzoylated-DEAE-cellulose with NaCl and caffeine solutions respectively. Other studies using bacterical and yeast DNA suggested that the first fraction contains native DNA, whereas the second may exhibit some degree of single-stranded character. In the present experiments, chromatography of DNA was monitored by labelling in vivo with [methyl-3H]thymidine in rats previously subjected to partial hepatectomy. In animals killed up to 1 h after thymidine injection, radioactivity eluted in the second fraction was inversely related to the incorporation time, being greatest when animals were killed 10 min after radioisotope injection. However, for most experiments, animals were allowed to survive 2-4 weeks after surgery before use, analysis being made on non-dividing DNA. Under these conditions, the proportion of caffeine-eluted DNA was decreased by subjecting the preparation to shear, before chromatography. A procedure that resulted in 12% of the recovered radioactivity being eluted with caffeine was adopted for experiments involving comparisons of the two DNA fractions. Under these conditions, cross-contamination could be detected by rechromatography, but this did not preclude distinction being made between the two fractions in terms of DNA structure. NaCl-eluted DNA did not bind to nitrocellulose filters. Caffeine-eluted DNA was retained by the filters and released by washing with 3mM-Tris/HCl, pH9.4. The fractions did not differ in terms of isopycnic centrifugation in CsCl. The NaCl-eluted fraction migrated as a single band in polyacrylamide gels, and this pattern was not modified by prior digestion with Neurospora crassa endonuclease. In contrast, caffeine-eluted DNA contained a minor component having a wide molecular-weight distribution and was subject to limited digestion by the endonuclease. The kinetics of denaturation of NaCi-eluted DNA in the presence of formaldehyde, in common with unfractionated DNA, were consistent with double-stranded structure. The same analysis of caffeine-eluted DNA revealed structural abnormality equivalent to two defects per 10000 base-pairs. The data are consistent with the minor fraction of rat liver DNA, separated by using benzoylated-DEAE-cellulose, containing regions of local denaturation. We previously showed that administration of the hepatocarcinogen dimethylnitrosamine is associated with an increase in the proportion of caffeine-eluted DNA. In terms of most analysis, differences between DNA fraction from nitrosamine-treated rats were similar to differences exhibited by preparations from control animals. However, structural analysis using denaturation kinetics indicated defects in both the NaCl- and caffeine-eluted DNA isolated from nitrosamine-treated rats. The two fractions differed from each other in that caffeine-eluted DNA exhibited a degree of structural damage far greater than that detected in any preparation from control animals...

Functional and structural changes in liver mitochondria of rats due to CCl4 intoxication—I

1971 ◽  
Vol 20 (7) ◽  
pp. 1437-1441 ◽  
Author(s):  
V.V. Lyachovich ◽  
V.M. Mishin ◽  
A.V. Dolgov ◽  
I.B. Tsyrlov
Keyword(s):  
Structural Changes ◽  
Liver Mitochondria ◽  
Ccl4 Intoxication
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