scholarly journals Tissue specific peculiarities of vibration-induced hypoxia of the rabbit heart, liver and kidney

2016 ◽  
Vol 14 (1) ◽  
pp. 46-62 ◽  
Author(s):  
Viktoriya V Vorobieva ◽  
Petr D Shabanov
Keyword(s):  
Succinic Acid ◽  
Energy Production ◽  
Pharmacological Action ◽  
Rabbit Heart ◽  
Tissue Type ◽  
Metabolic States ◽  
Before And After ◽  
Liver And Kidney ◽  
Endogenous Substrates

The purpose of the paper was experimental study of activity of energy production of the heart, liver and kidney after harmful action of general vibration with 8 and 44 Hz frequency. The functional state of native mitochondria in tissue homogenates was studied by polarographic method by means of closed oxygen device of halvanic type in thermostated cuvette of 1 ml volume in the salt medium of incubation. Metabolic states of mitochondria of the rabbit heart, liver and kidney were modeled in vitro in oxidation of endogenous substrates (before and after administration of inhibitors of different stages of breath chain) varying exogenous substrates (before and after administration of 2.4-DNP into the cell). In order to synchronize the changes in short time, the incomplete cycle of metabolic states “endogenous breath → rest → activity” was used. The velocity of mitochondrial oxidation of endogenous substrates was determined by tissue type, and was 16.3 ± 4.3, 5.2 ± 0.6 and 8.13 ± 1.4 ng-atom О min-1mg-1 protein for the heart, liver and kidney of intact animals respectively. In the heart, after high frequent vibration, the reduction of oxidation velocity of NAD-dependent substrates in rest and in active metabolic state of mitochondria was 43 % (р ≤ 0.05) and 30 % (р ≤ 0.01) respectively, while the velocity of oxidation for endogenous succinic acid increased by 77 % (р ≤ 0.05) to 21st session of vibration, then constantly decreasing to the end of vibration sessions. The same changes but in less degree were registerted in the liver and kidney. The systems of energy production of the heart and the studied parenchimatic organs were involved in reaction on vibration exposure and reacted typically by low energetic shift with hyperactivation of endogenous succinic acid system of oxidation and inhibition of NAD-depended part of the breath chain of mitochondria. Therefore, the study of bioenergetics mechanisms of hypoxia in different tissues allows to clear the molecular targets for pharmacological action by means of substrate antihypoxants.

Abstract 118: Nebivolol Therapy Enhances Endothelial Fibrinolytic Capacity in Adults with Elevated Blood Pressure

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Christopher A DeSouza ◽  
Tyler D Bammert ◽  
Kyle J Diehl ◽  
Caitlin A Dow ◽  
Jared J Greiner ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Elevated Blood Pressure ◽  
Tissue Type ◽  
Elevated Blood ◽  
Thrombotic Risk ◽  
Type Plasminogen Activator ◽  
Before And After ◽  
Middle Aged Adults

Impaired endothelial fibrinolytic function contributes to increased thrombotic risk with elevated blood pressure . In vitro data suggests that the antihypertensive, nebivolol (N), favorably effects the fibrinolytic system, but there is no in vivo clinical evidence that N treatment improves endothelial fibrinolytic function. We hypothesized that chronic N therapy will increase the capacity of the endothelium to release tissue-type plasminogen activator (t-PA) in adults with elevated blood pressure (BP ≥ 130/85 mm Hg). In an ongoing study, 36 middle-aged adults (age: 44-67 years) were treated for 12 weeks: 12 with N (5 mg/d; BP 141/86±2/2 mmHg); 12 with metoprolol succinate (M: 100 mg/d; 140/90±3/2 mmHg); and 12 with placebo (P; 138/85±2/2 mmHg). Before and after intervention, net endothelial release of t-PA was determined, in vivo , in response to intrabrachial infusions of bradykinin (BK: 125-500 ng/min) and sodium nitroprusside (SNP: 2-8 μg/min). Subject characteristics (age, BMI, systolic and diastolic BP) were similar between the groups. Blood pressure was lowered (P< 0.05) to a similar extent by both N (124/78±3/2 mmHg) and M (124/78±3/1 mmHg) but unchanged by P (134/80±3/2 mmHg). Endothelial t-PA release in response to BK was not significantly different between the N (-2.8±1.4 to 49.2±5.6 ng/100 mL tissue/min), M (-0.5±1.3 to 53.5±8.5 ng/100 mL tissue/min) and P (0.1±1.1 to 52.0±5.6 ng/100 mL tissue/min) groups prior to intervention. After intervention, only N therapy affected t-PA release; the capacity of the endothelium to release t-PA in the N group was significantly higher (-1.9±1.6 to 72.6±7.1 ng/100 mL tissue/min; P< 0.05). Total amount of t-PA released (area under the BK curve) markedly increased (45%) in response to N (308±39 vs 445±47 ng/100 mL tissue; P< 0.05). In contrast, endothelial t-PA release was not significantly altered by M (-1.6±1.1 to 54.0±6.1 ng/100 mL tisuue/min). As expected, t-PA release was unchanged with P. These results demonstrate that, in spite of similar reductions in blood pressure, N, but not M, treatment increases the capacity of the endothelium to release t-PA in adults with elevated blood pressure. Enhanced endothelial fibrinolytic function with N may provide an important vascular benefit in this at risk population.

scholarly journals In vitro and in vivo effects of 3-bromopyruvate against Echinococcus metacestodes

2019 ◽  
Vol 50 (1) ◽  
Author(s):  
Qi Xin ◽  
Miaomiao Yuan ◽  
Huanping Li ◽  
Xiaoxia Song ◽  
Jun Lu ◽  
...  
Keyword(s):  
Energy Production ◽  
Alveolar Echinococcosis ◽  
Weekly Treatment ◽  
Significant Toxicity ◽  
Liver And Kidney ◽  
In Vitro Effects ◽  
In Vivo Effects ◽  
Dose Dependent

AbstractWhile searching for novel anti-echinococcosis drugs, we have been focusing on glycolysis which is relied on by Echinococcus for energy production and intermediates for other metabolic processes. The aim of this study was to investigate the potential therapeutic implication of glycolytic inhibitors on Echinococcus. Our results demonstrate that at an initial concentration of 40 μM, all inhibitors of glycolysis used in the current experiment [3-bromopyruvate (3-BrPA), ornidazole, clorsulon (CLS), sodium oxamate and 2,6-dihydroxynaphthalene (NA-P2)] show considerable in vitro effects against Echinococcus granulosus protoscoleces and Echinococcus multilocularis metacestodes. Among them, 3-BrPA exhibited the highest activity which was similar to that of nitazoxanide (NTZ) and more efficacious than albendazole (ABZ). The activity of 3-BrPA was dose dependent and resulted in severe ultrastructural destructions, as visualized by electron microscopy. An additional in vivo study in mice infected with E. multilocularis metacestodes indicates a reduction in parasite weight after the twice-weekly treatment of 25 mg/kg 3-BrPA for 6 weeks, compared to that of the untreated control. In particular, in contrast to ABZ, the administration of 25 mg/kg 3-BrPA did not cause toxicity to the liver and kidney in mice. Similarly, at the effective dose against Echinococcus larvae, 3-BrPA showed no significant toxicity to human hepatocytes. Taken together, the results suggest that interfering with the glycolysis of the parasite may be a novel chemotherapeutical option and 3-BrPA, which exhibited a remarkable activity against Echinococcus, may be a promising potential drug against cystic echinococcosis (CE) and alveolar echinococcosis (AE).

scholarly journals Cellular mechanisms of hypoxia development in the tissues of experimental animals under varying characteristics of vibration exposure

2019 ◽  
Vol 17 (3) ◽  
pp. 59-70
Author(s):  
Viktoriya V. Vorobieva ◽  
Petr D. Shabanov
Keyword(s):  
Kinetic Parameters ◽  
Oxidation Rate ◽  
Oxygen Sensor ◽  
Tissue Homogenate ◽  
Endogenous Respiration ◽  
Experimental Animals ◽  
Oxidation Rates ◽  
Metabolic States ◽  
Before And After ◽  
Endogenous Substrates

The aim of the work was to study the primary bioenergetic mechanisms of hypoxia formation in the myocardial tissue of experimental animals depending on the differentiated physical characteristics of vibration (frequency and duration) and their combination. The study of the functional states of native mitochondria in the composition of the tissue homogenate was carried out using the polarographic method and a galvanic-type closed-oxygen sensor in a 1-ml thermostatic cuvette in a salt incubation medium. The metabolic states of the mitochondria of the myocardium of experimental animals were modeled in vitro during the oxidation of endogenous substrates (before and after the administration of inhibitors of different links of the respiratory chain), with varying exogenous energy substrates (before and after the introduction of 2,4-DNP into the cell). In order to ensure synchronism of measurements in a short time, an incomplete cycle of metabolic states “endogenous respiration → rest → activity” was used. The results of multiple comparisons of variations in kinetic parameters revealed a reliable but multidirectional effect of the frequency of vibration on the rate of oxidation of substrates of the mitochondria of the heart of rabbits in different metabolic states. A change in the duration of exposure to vibration showed an increase in the oxidation rate of endogenous substrates and succinic acid at rest to 21–56 sessions by 17% and 24. 4%, respectively, while the oxidation rate of glutamate decreased to 56 sessions by 24. 5%. Comparison of the general variability of kinetic parameters with a combination of frequency and duration of vibration at different levels of variation showed that it was the interaction of factors that made the most important and significant contribution to the intergroup variability of oxidation rates of endogenous and exogenous substrates, identifying signs of the formation of bioenergetic hypoxia and allowing analysis of the primary physical transformation phenomena in the biological effect.

Electron microscopic study of the membrane glycoproteins in the rat kidney after cisplatin treatment

1989 ◽  
Vol 47 ◽  
pp. 912-913
Author(s):  
S.K. Aggarwal
Keyword(s):  
Alkaline Phosphatase ◽  
Rat Kidney ◽  
Light And Electron Microscopy ◽  
Kidney Tissue ◽  
Membrane Glycoproteins ◽  
Electron Microscopic ◽  
Before And After ◽  
Interstrand Cross Links ◽  
Cross Links

The proposed primary mechanism of action of the anticancer drug cisplatin (Cis-DDP) is through its interaction with DNA, mostly through DNA intrastrand cross-links or DNA interstrand cross-links. DNA repair mechanisms can circumvent this arrest thus permitting replication and transcription to proceed. Various membrane transport enzymes have also been demonstrated to be effected by cisplatin. Glycoprotein alkaline phosphatase was looked at in the proximal tubule cells before and after cisplatin both in vivo and in vitro for its inactivation or its removal from the membrane using light and electron microscopy.Outbred male Swiss Webster (Crl: (WI) BR) rats weighing 150-250g were given ip injections of cisplatin (7mg/kg). Animals were killed on day 3 and day 5. Thick slices (20-50.um) of kidney tissue from treated and untreated animals were fixed in 1% buffered glutaraldehyde and 1% formaldehyde (0.05 M cacodylate buffer, pH 7.3) for 30 min at 4°C. Alkaline phosphatase activity and carbohydrates were demonstrated according to methods described earlier.

Structural integrity after cold storage of human epidermal model in hypothermosol: A correlative ultrastructural and fluorescent assay

1994 ◽  
Vol 52 ◽  
pp. 270-271
Author(s):  
Henry H. Eichelberger ◽  
John G. Baust ◽  
Robert G. Van Buskirk
Keyword(s):  
Cold Storage ◽  
Structural Integrity ◽  
Culture Media ◽  
Cell Structure ◽  
Natural State ◽  
Sodium Cacodylate ◽  
Ruthenium Tetroxide ◽  
Cacodylate Buffer ◽  
Before And After

For research in cell differentiation and in vitro toxicology it is essential to provide a natural state of cell structure as a benchmark for interpreting results. Hypothermosol (Cryomedical Sciences, Rockville, MD) has proven useful in insuring the viability of synthetic human epidermis during cold-storage and in maintaining the epidermis’ ability to continue to differentiate following warming.Human epidermal equivalent, EpiDerm (MatTek Corporation, Ashland, MA) consisting of fully differentiated stratified human epidermal cells were grown on a microporous membrane. EpiDerm samples were fixed before and after cold-storage (4°C) for 5 days in Hypothermosol or skin culture media (MatTek Corporation) and allowed to recover for 7 days at 37°C. EpiDerm samples were fixed 1 hour in 2.5% glutaraldehyde in sodium cacodylate buffer (pH 7.2). A secondary fixation with 0.2% ruthenium tetroxide (Polysciences, Inc., Warrington, PA) in sodium cacodylate was carried out for 3 hours at 4°C. Other samples were similarly fixed, but with 1% Osmium tetroxide in place of ruthenium tetroxide. Samples were dehydrated through a graded acetone series, infiltrated with Spurrs resin (Polysciences Inc.) and polymerized at 70°C.

Inhibitory effects of bioaccessible anthocyanins and procyanidins from apple, red grape, cinnamon on α-amylase, α-glucosidase and lipase

2020 ◽  
pp. 1-9
Author(s):  
Pınar Ercan ◽  
Sedef Nehir El
Keyword(s):  
Inhibitory Activity ◽  
Digestive Enzymes ◽  
Positive Control ◽  
Anthocyanin Content ◽  
Inhibitory Effects ◽  
Total Anthocyanin ◽  
Total Anthocyanin Content ◽  
Before And After ◽  
Red Grape

Abstract. The goals of this study were to determine and evaluate the bioaccessibility of total anthocyanin and procyanidin in apple (Amasya, Malus communis), red grape (Papazkarası, Vitis vinifera) and cinnamon (Cassia, Cinnamomum) using an in vitro static digestion system based on human gastrointestinal physiologically relevant conditions. Also, in vitro inhibitory effects of these foods on lipid (lipase) and carbohydrate digestive enzymes (α-amylase and α-glucosidase) were performed with before and after digested samples using acarbose and methylumbelliferyl oleate (4MUO) as the positive control. While the highest total anthocyanin content was found in red grape (164 ± 2.51 mg/100 g), the highest procyanidin content was found in cinnamon (6432 ± 177.31 mg/100 g) (p < 0.05). The anthocyanin bioaccessibilities were found as 10.2 ± 1%, 8.23 ± 0.64%, and 8.73 ± 0.70% in apple, red grape, and cinnamon, respectively. The procyanidin bioaccessibilities of apple, red grape, and cinnamon were found as 17.57 ± 0.71%, 14.08 ± 0.74% and 18.75 ± 1.49%, respectively. The analyzed apple, red grape and cinnamon showed the inhibitory activity against α-glucosidase (IC50 544 ± 21.94, 445 ± 15.67, 1592 ± 17.58 μg/mL, respectively), α-amylase (IC50 38.4 ± 7.26, 56.1 ± 3.60, 3.54 ± 0.86 μg/mL, respectively), and lipase (IC50 52.7 ± 2.05, 581 ± 54.14, 49.6 ± 2.72 μg/mL), respectively. According to our results apple, red grape and cinnamon have potential to inhibit of lipase, α-amylase and α-glucosidase digestive enzymes.

Cardioprotection with Captopril added to Bretschneider-Solution: An in vitro rabbit heart study

2014 ◽  
Vol 62 (S 01) ◽  
Author(s):  
A. Hoyer ◽  
P. Pritzwald-Stegmann ◽  
J. Kempfert ◽  
C. Etz ◽  
F.W. Mohr ◽  
...  
Keyword(s):  
Rabbit Heart ◽  
Heart Study

Fibrin-specificity of a Plasminogen Activator Affects the Efficiency of Fibrinolysis and Responsiveness to Ultrasound: Comparison of Nine Plasminogen Activators In Vitro

1999 ◽  
Vol 81 (04) ◽  
pp. 605-612 ◽  
Author(s):  
Dmitry V. Sakharov ◽  
Marrie Barrett-Bergshoeff ◽  
Rob T. Hekkenberg ◽  
Dingeman C. Rijken
Keyword(s):  
Thrombolytic Therapy ◽  
Plasminogen Activator ◽  
Tissue Type ◽  
Bolus Administration ◽  
High Frequency Ultrasound ◽  
Single Chain ◽  
Response Curves ◽  
Maximal Speed ◽  
Frequency Ultrasound

SummaryIn a number of cases, thrombolytic therapy fails to re-open occluded blood vessels, possibly due to the occurrence of thrombi resistant to lysis. We investigated in vitro how the lysis of hardly lysable model thrombi depends on the choice of the plasminogen activator (PA) and is accelerated by ultrasonic irradiation. Lysis of compacted crosslinked human plasma clots was measured after addition of nine different PAs to the surrounding plasma and the effect of 3 MHz ultrasound on the speed of lysis was assessed.Fibrin-specific PAs showed bell-shaped dose-response curves of varying width and height. PAs with improved fibrin-specificity (staphylokinase, the TNK variant of tissue-type PA [tPA], and the PA from the saliva of the Desmodus rotundus bat) induced rapid lysis in concentration ranges (80-, 260-, and 3,500-fold ranges, respectively) much wider than that for tPA (a 35-fold range). However, in terms of speed of lysis, these three PAs exceeded tPA only slightly. Reteplase and single-chain urokinase were comparable to tPA, whereas two-chain urokinase, anistreplase, and streptokinase were inferior to tPA. In the case of fibrin-specific PAs, ultrasonic treatment accelerated lysis about 1.5-fold. For streptokinase no acceleration was observed. The effect of ultrasound correlated with the presence of plasminogen in the outer plasma, suggesting that it was mediated by facilitating the transport of plasminogen to the surface of the clot.In conclusion, PAs with improved fibrin-specificity induce rapid lysis of plasminogen-poor compacted plasma clots in much wider concentration ranges than tPA. This offers a possibility of using single-or double-bolus administration regimens for such PAs. However, it is not likely that administration of these PAs will directly cause a dramatic increase in the rate of re-opening of the occluded arteries since they are only moderately superior to tPA in terms of maximal speed of lysis. Application of high-frequency ultrasound as an adjunct to thrombolytic therapy may increase the treatment efficiency, particularly in conjunction with fibrin-specific PAs.

Radiolabeled r-Hirudin as a Measure of Thrombin Activity at, or within, the Rabbit Aorta Wall In Vitro and In Vivo

1994 ◽  
Vol 71 (04) ◽  
pp. 499-506 ◽  
Author(s):  
Mark W C Hatton ◽  
Bonnie Ross-Ouellet
Keyword(s):  
Rabbit Aorta ◽  
Balloon Injury ◽  
Recombinant Hirudin ◽  
Aorta Wall ◽  
Thrombin Activity ◽  
Before And After ◽  
The Matrix

SummaryThe behavior of 125I-labeled recombinant hirudin towards the uninjured and de-endothelialized rabbit aorta wall has been studied in vitro and in vivo to determine its usefulness as an indicator of thrombin activity associated with the aorta wall. Thrombin adsorbed to either sulfopropyl-Sephadex or heparin-Sepharose bound >95% of 125I-r-hirudin and the complex remained bound to the matrix. Binding of 125I-r-hirudin to the exposed aorta subendothelium (intima-media) in vitro was increased substantially if the tissue was pre-treated with thrombin; the quantity of l25I-r-hirudin bound to the de-endothelialized intima-media (i.e. balloon-injured in vitro) correlated positively with the quantity of bound 131I-thrombin (p <0.01). Aortas balloon-injured in vivo were measured for thrombin release from, and binding of 125I-r-hirudin to, the de-endothelialized intimal surface in vitro; 125I-r-hirudin binding correlated with the amount of active thrombin released (p <0.001). Uptake of 125I-r-hirudin by the aorta wall in vivo was proportional to the uptake of 131I-fibrinogen (as an indicator of thrombin activity) before and after balloon injury. After 30 min in the circulation, specific 125I-r-hirudin binding to the uninjured and de-endo- thelialized (at 1.5 h after injury) aorta wall was equivalent to 3.4 (± 2.5) and 25.6 (±18.1) fmol of thrombin/cm2 of intima-media, respectively. Possibly, only hirudin-accessible, glycosaminoglycan-bound thrombin is measured in this way.

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