scholarly journals Lactate dehydrogenase activity staining demonstrates time-dependent immune cell infiltration in human ex-vivo burn-injured skin

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Joshua Cuddihy ◽  
Gongjie Wu ◽  
Laptin Ho ◽  
Hiromi Kudo ◽  
Andreas Dannhorn ◽  
...  

AbstractBurn injuries constitute one of the most serious accidental injuries. Increased metabolic rate is a hallmark feature of burn injury. Visualising lactate dehydrogenase (LDH) activity has been previously used to identify metabolic activity differences, hence cell viability and burn depth in burn skin. LDH activity was visualised in injured and uninjured skin from 38 sub-acute burn patients. LDH activity aided the identification of spatially correlating immunocompetent cells in a sub-group of six patients. Desorption Electrospray Ionisation Mass Spectrometry Imaging (DESI MSI) was used to describe relative lactate and pyruvate abundance in burned and uninjured tissue. LDH activity was significantly increased in the middle and deep regions of burnt skin compared with superficial areas in burnt skin and uninjured tissue and positively correlated with post-burn time. Regions of increased LDH activity showed high pyruvate and low lactate abundance when examined with DESI-MSI. Areas of increased LDH activity exhibited cellular infiltration, including CD3 + and CD4 + T-lymphocytes and CD68 + macrophages. Our data demonstrate a steady increase in functional LDH activity in sub-acute burn wounds linked to cellular infiltration. The cell types associated are related to tissue restructuring and inflammation. This region in burn wounds is likely the focus of dysregulated inflammation and hypermetabolism.

Sensors ◽  
2019 ◽  
Vol 19 (9) ◽  
pp. 2089 ◽  
Author(s):  
Yael Adler-Levy ◽  
Atara Nardi-Schreiber ◽  
Talia Harris ◽  
David Shaul ◽  
Sivaranjan Uppala ◽  
...  

[1-13C]pyruvate, the most widely used compound in dissolution-dynamic nuclear polarization (dDNP) magnetic resonance (MR), enables the visualization of lactate dehydrogenase (LDH) activity. This activity had been demonstrated in a wide variety of cancer models, ranging from cultured cells, to xenograft models, to human tumors in situ. Here we quantified the LDH activity in precision cut tumor slices (PCTS) of breast cancer xenografts. The Michigan Cancer Foundation-7 (MCF7) cell-line was chosen as a model for the luminal breast cancer type which is hormone responsive and is highly prevalent. The LDH activity, which was manifested as [1-13C]lactate production in the tumor slices, ranged between 3.8 and 6.1 nmole/nmole adenosine tri-phosphate (ATP) in 1 min (average 4.6 ± 1.0) on three different experimental set-ups consisting of arrested vs. continuous perfusion and non-selective and selective RF pulsation schemes and combinations thereof. This rate was converted to an expected LDH activity in a mass ranging between 3.3 and 5.2 µmole/g in 1 min, using the ATP level of these tumors. This indicated the likely utility of this approach in clinical dDNP of the human breast and may be useful as guidance for treatment response assessment in a large number of tumor types and therapies ex vivo.


Gene Therapy ◽  
2021 ◽  
Author(s):  
Jeremy Epah ◽  
Richard Schäfer

AbstractHematopoietic stem cell transplantation (HSCT) is the therapeutic concept to cure the blood/immune system of patients suffering from malignancies, immunodeficiencies, red blood cell disorders, and inherited bone marrow failure syndromes. Yet, allogeneic HSCT bear considerable risks for the patient such as non-engraftment, or graft-versus host disease. Transplanting gene modified autologous HSCs is a promising approach not only for inherited blood/immune cell diseases, but also for the acquired immunodeficiency syndrome. However, there is emerging evidence for substantial heterogeneity of HSCs in situ as well as ex vivo that is also observed after HSCT. Thus, HSC gene modification concepts are suggested to consider that different blood disorders affect specific hematopoietic cell types. We will discuss the relevance of HSC heterogeneity for the development and manufacture of gene therapies and in exemplary diseases with a specific emphasis on the key target HSC types myeloid-biased, lymphoid-biased, and balanced HSCs.


10.23856/3305 ◽  
2019 ◽  
Vol 33 (2) ◽  
pp. 50-55
Author(s):  
Olena Konovalova

The changes of activity of LDH and its isoenzymatic fractions under load with lead acetate are described. The introduction of a subacute dose of Pb2 + led to a decrease in the LDH activity of the rat liver and an increase in the heart. Preliminary introduction of small doses of Pb2 + partially prevents increased LDH activity in the heart and completely inhibits its increase in the liver. The proportion of urea-stable fraction in the heart and blood serum is significantly increased, indicating an increase in the aerobic direction of energy metabolism. The obtained results are the experimental substantiation of further investigations of influence mechanism of heavy metals on the organism, as well as the motivation to prevent environmental pollution by man-made xenobiotics.


2017 ◽  
Vol 2017 ◽  
pp. 1-6
Author(s):  
Yoichi Kawamura ◽  
Seiichiro Takeshita ◽  
Takashi Kanai ◽  
Mari Takizawa ◽  
Yusuke Yoshida ◽  
...  

Abnormal urinary findings, such as sterile pyuria, proteinuria, and microscopic hematuria, are often seen in the acute phase of Kawasaki disease (KD). We investigated the potential significance of urinary lactate dehydrogenase (U-LDH) activity and its isozyme patterns in KD. Total U-LDH activity and its isozymes (U-LDH1-5) levels were compared among 120 patients with KD, 18 patients with viral infection (VI), and 43 patients with upper urinary tract infection (UTI) and additionally compared between intravenous immunoglobulin (IVIG) responders (n=89) and nonresponders (n=31) with KD. Total U-LDH activity was higher in KD (35.4±4.8 IU/L, P<0.05) and UTI patients (66.0±8.0 IU/L, P<0.01) than in VI patients (17.0±6.2 IU/L). In the isozyme pattern analysis, KD patients had high levels of U-LDH1 and U-LDH2, while UTI patients had high levels of U-LDH3, U-LDH4, and U-LDH5. Furthermore, IVIG nonresponders of KD had significantly higher levels of total U-LDH activity (45.1±4.7 IU/L, P<0.05), especially U-LDH1 and U-LDH2 (P<0.05), than IVIG responders (32.0±2.8 IU/L). KD patients have increased levels of total U-LDH activity, especially U-LDH-1 and U-LDH2, indicating a unique pattern of U-LDH isozymes different from that in UTI patients.


1973 ◽  
Vol 82 (2) ◽  
pp. 192-195 ◽  
Author(s):  
S. K. Juhn ◽  
John S. Huff ◽  
Michael M. Paparella

Biochemical characteristics of middle ear effusions (MEE) should provide a better understanding of the etiopathogenesis of serous otitis media. In order to develop another parameter for the biochemical characterization of the MEE, lactate dehydrogenase (LDH) and LDH isoenzyme patterns in the serous middle ear effusion and serum from 20 patients with serous otitis media were compared. The LDH activity was measured by the usual spectrophotometric method. The isoenzyme patterns were compared on electropherograms using cellulose polyacetate strips. The LDH activity in MEE was significantly higher (P < 0.001) than it was in serum. Fractions of isoenzymes 1 and 2 were each smaller in MEE than in serum. Isoenzymes 4 and 5 have a significantly higher (P < 0.001) fraction in MEE than in serum. Since LDH is an intracellular enzyme and middle ear mucosa is reported to have high content of isoenzymes 4 and 5, the inflammatory changes in the middle ear mucosa which may release intracellular LDH, are suggested as the cause of both higher activity of LDH and the higher fractions of isoenzymes 4 and 5 in MEE than those in the serum.


Biomedicines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1323
Author(s):  
Li-Jie Hsu ◽  
Chao-Lin Liu ◽  
Ming-Ling Kuo ◽  
Chia-Ning Shen ◽  
Chia-Rui Shen

Cell therapy is usually defined as the treatment or prevention of human disease by supplementation with cells that have been selected, manipulated, and pharmacologically treated or altered outside the body (ex vivo). Induced pluripotent stem cells (iPSCs), with their unique characteristics of indefinite expansion in cultures and genetic modifications, represent an ideal cell source for differentiation into specialized cell types. Cell therapy has recently become one of the most promising therapeutic approaches for cancers, and different immune cell types are selected as therapeutic platforms. Natural killer (NK) cells are shown to be effective tumor cell killers and do not cause graft-vs-host disease (GVHD), making them excellent candidates for, and facilitating the development of, “off-the-shelf” cell therapies. In this review, we summarize the progress in the past decade in the advent of iPSC technology and review recent developments in gene-modified iPSC-NK cells as readily available “off-the-shelf” cellular therapies.


2005 ◽  
Vol 15 (3) ◽  
pp. 438-444 ◽  
Author(s):  
Š. ŠIMAGA ◽  
M. Osmak ◽  
D. Babič ◽  
M. ŠPREM ◽  
B. Vukelič ◽  
...  

In an attempt to identify glycolytic capacity of normal and neoplastic human ovary, total lactate dehydrogenase (LDH) activity was measured in tissue cytosol originating from 69 patients (18 with benign ovarian tumor, 34 with ovarian carcinoma, six with nonepithelial ovarian malignant tumors, and 11 with tumor metastatic to ovary) and compared to the LDH activity of normal ovarian tissues (n = 19). Median value of total LDH-specific activity expressed as U/mg protein was 0.546 in normal tissues, 0.584 in benign tumors, 1.071 in malignancies metastatic to ovaries, 0.872 in nonepithelial primary ovarian tumors, and 0.818 in primary carcinomas. A significant rise in LDH-specific activity was found in malignant primary and secondary tumors of epithelial and nonepithelial origin, but not in benign neoplasms, compared to the activity in normal tissue. Ovarian carcinomas of serous histologic type did not differ in LDH activity from mucinous tumors. However, poorly differentiated carcinomas (grade 3) showed significantly enhanced activity of this glycolytic enzyme when compared to its grade 1 counterpart. The subgroup of grade 1 tumors did not differ in LDH activity from normal and benign ovarian tissue. Obtained results suggest that direct correlation might exist between ovarian epithelial tumor grade and lactate dehydrogenase activity.


2021 ◽  
pp. 039139882199066
Author(s):  
Katharina Kalka ◽  
Zoe Keldenich ◽  
Henning Carstens ◽  
Björn Walter ◽  
Ursula Rauen ◽  
...  

Introduction: Ex vivo lung perfusion (EVLP) is an established technique to evaluate and eventually recondition lungs prior to transplantation. Custodiol-MP (C-MP) solution is a new solution, designed for clinical machine perfusion, that has been used for kidneys. The aim of this study was to compare the effects of EVLP with Custodiol-MP on lung functional outcomes to the gold standard of EVLP with Steen Solution™. Material and Methods: In a porcine EVLP model of DCDD (Donation after Circulatory Determination of Death), lungs were perfused with Steen Solution™ (SS, n = 7) or Custodiol-MP solution supplemented with 55 g/l albumin (C-MP, n = 8). Lungs were stored cold for 4 h in low potassium dextran solution and subsequently perfused ex vivo for 4 h. During EVLP pulmonary gas exchange, activities of lactate dehydrogenase (LDH) and alkaline phosphatase (AP) as well as levels of lactate in the perfusate were recorded hourly. Results: Oxygenation capacity differed significantly between groups (averaged over 4 h: SS 274 ± 178 mmHg; C-MP 284 ± 151 mmHg p = 0.025). Lactate dehydrogenase activities and lactate concentrations were significantly lower in Custodiol-MP perfused lungs. In a porcine model of DCDD with 4 h of EVLP the use of modified Custodiol-MP as perfusion solution was feasible. The use of C-MP showed at least comparable lung functional outcomes to the use of Steen SolutionTM. Furthermore C-MP perfusion resulted in significantly lower lactate dehydrogenase activity and lactate levels in the perfusate and higher oxygenation capacity.


2016 ◽  
Vol 73 (9) ◽  
pp. 1389-1394 ◽  
Author(s):  
Frédéric Laberge ◽  
Nicholas Edmunds ◽  
Irene Yin-Liao ◽  
Kevin S. McCann

The activity of muscle glycolytic enzymes scales positively with body size in active fish, a phenomenon thought to counter the increased costs of burst swimming faced by larger individuals. Recent work argued that changes in these enzymes during ontogeny additionally reflect changes in foraging ecology. Here, we evaluated the relationship between muscle anaerobic metabolism and foraging ecology in a population of wild smallmouth bass (Micropterus dolomieu) by relating activity of muscle lactate dehydrogenase (LDH) to estimates of trophic position and habitat use obtained from stable isotope signatures. As expected, LDH activity increased with body size. However, further analysis showed associations between foraging ecology and LDH activity. Specifically, a shift to higher trophic position, indicating a change in diet, was paralleled by a shift to increased LDH activity. However, a steady mass-specific decrease in LDH activity was observed as the fish grew above the size associated with this diet shift. Further, lower LDH activity was associated with increasing use of littoral carbon sources. These findings contribute to our understanding of how plasticity in muscle anaerobic potential is associated with fish foraging ecology.


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