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Results for “Creatine Kinase, MM Form”

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PubMed1974

Calcium-activated tension of skinned muscle fibers of the frog. Dependence on magnesium adenosine triphosphate concentration.

The influence of MgATP on the Ga(++)-activated isometric tension of skinned frog muscle fibers was examined in solutions containing: Mg(++) = 5 mM, creatine phosphate (CP) = 14.5 mM, creatinephosphokinase (CPK) = 1 mg/ml, total EGTA = 7 mM, CaCl(2), KCl, imidazole >/= 20 mM so that ionic strength = 0.15, pH = 7.00, and MgATP = 2 mM, 0.1 mM, or 20 microM. CP and CPK were necessary for these experiments as determined experimentally by their effect on the tension-Ca(++) relation, which was saturated for CP >/= 14.5 mM. This was interpreted to mean that sufficient CP was present to effectively buffer MgATP intracellularly. Decreasing MgATP shifts the tension-pCa curve to higher pCa (-log Ca(++)) so that, for half-maximal tension: pCa(1/2) = 4.5 for MgATP = 2 mM, pCa(1/2) = 5.1 for MgATP = 0.1 mM, and pCa(1/2) = 5.8 for MgATP = 20 microM; maximum isometric tension is the same in all cases, however. If MgATP was decreased to 1 microM, tension at Ga(++) > 10(-8) M was 84% of the maximum Ca(-+)-activated tension in 2 mM MgATP and increased only slightly to 90% for pCa = 4.5. Weber (1970, In The Physiology and Biochemistry of Muscle as Food, Volume 2, E. J. Briskey, R. G. Cassens, and B. B. Marsh, University of Wisconsin Press, Madison, Wis.), using similar solutions, observed similar shifts in half-maximal calcium activation of rabbit myofibril ATPase rates. In explanation, Weber and Bremel (1971, In Contractility of Muscle Cells and Related Processes, R. J. Podolsky, editor, Prentice-Hall, Inc., Englewood Cliffs, N.J.; Bremel and Weber, 1972, Nat. New Biol., 238:97) have described a mechanism whereby, at low ATP, "rigor complexes" are formed between myosin and thin filament actin and, in turn, alter the calcium affinity of one class of the two Ca(++)-binding sites on troponin, so that the thin filament is "turned on" for contraction at lower Ca(++) levels. Tension data from skinned fibers substantially supports this hypothesis. A stability constant for CaEGTA of 2.62 x 10(10) M(-1) was determined, with the help of F. N. Briggs, in solutions similar to those used for skinned fibers and was the same for 100 and 300 mM KCl.

Adenosine Triphosphate↗

PubMed1974

Kinetic properties of the isoenzymes of human creatine phosphokinase.

Studies of the three human creatine phosphokinase (EC 2.7.3.2) isoenzymes, MM, MB, and BB, show that important differences exist in substrate dependency of the reaction rates. A method was developed to study these properties in which the ATP formed in the reverse reaction was measured by means of firefly luciferase. With substrate conditions at which the isoenzymes showed substantial differences in activity the method could be used for the detection of changes in the isoenzyme pattern of the serum of patients with an acute myocardial infarction. The MB isoenzyme appearing in this condition could be detected quantitatively.

Adenosine Triphosphate↗

PubMed1994

Quantification and removal of glycogen phosphorylase and other enzymes associated with sarcoplasmic reticulum membrane preparations.

The enzymatic characterization of sarcoplasmic reticulum membrane fragments from rabbit skeletal muscle presented in this paper shows that glycogen phosphorylase, as well as other enzymes (e.g., creatine kinase, myokinase, phosphorylase kinase, glycosidase, AMP-deaminase, phosphoglucomutase) are associated with these membrane preparations. Amongst these enzymes, the highest activity associated with sarcoplasmic reticulum membranes is that of glycogen phosphorylase, which is mostly (at least 95%) in its b form (dephosphorylated form), since its activity in sarcoplasmic reticulum membranes is largely dependent upon AMP. A protocol is presented to quantify the amount of phosphorylase bound to sarcoplasmic reticulum membranes from fluorimetric measurements of the content of its coenzyme, pyridoxal 5'-phosphate. The content of phosphorylase ranged from 0.03 to 0.37 mg phosphorylase per mg of membrane protein, in sarcoplasmic reticulum membrane preparations made following several of the protocols most commonly used and also depending upon the length of the starvation period of the animal before killing. We also show that dilution of sarcoplasmic reticulum membranes to 0.1-0.2 mg protein per ml in a buffer containing 50 mM Tes-KOH (pH 7.4), 0.1 M KCl and 0.25 M sucrose removes at least 95% of glycogen phosphorylase from these membrane fragments, as well as other enzymes like myokinase and glycosidase. On these grounds, we suggest to introduce a final dilution step as indicated above in protocols of sarcoplasmic reticulum membrane preparations.

AMP Deaminase↗

PubMed2003

Once again about the functional coupling between mitochondrial creatine kinase and adenine nucleotide translocase.

The synthesis of creatine phosphate (CP) by mitochondrial creatine kinase during oxidative phosphorylation was terminated when the mass action ratio of the creatine kinase reaction Gamma = [ADP]*[CP]/[ATP]*[Cr] became equal to the apparent equilibrium constant (K(eq)(app))of this reaction. Subsequent excess of Gamma over the K(eq)(app) was due to an increase in the ADP concentration in the medium. A comparable increase in the ADP concentration also occurred in the absence of creatine (Cr) in the incubation medium. Increase in the ADP concentration was shown to be associated with a decrease in the rate of oxidative phosphorylation and with a relative increase in the ATPase activity of mitochondria during the incubation. A low concentration of ADP (<30 micro M) and relatively high concentrations (1-6 mM) of other components of the creatine kinase reaction prevented the detection of the reverse reaction within 10 min after Gamma exceeded the K(eq)(app), but the reverse reaction became evident on more prolonged incubation. The reverse reaction was accompanied by a further increase in Gamma. Low ADP concentration in the medium was also responsible for the lack of an immediate conversion of the excess creatine phosphate added although Gamma > K(eq)(app). The findings are concluded to be in contradiction with the concept of microcompartment formation between mitochondrial creatine kinase and adenine nucleotide translocase.

Adenosine Diphosphate↗

PubMed2006

[Macro creatine kinase: illness marker. Practical guide for the management].

BACKGROUND AND OBJECTIVE: The Macro creatine kinase (Macro-CK) is a complex constituted by polymerization of isoenzymes of creatine kinase (CK-BB or CK-MM together with IgG in the type I and oligomers of CK mitochondrial in the type II). Their presence in plasma generates false elevations of the CK-MB isoenzyme, upon interfering with the techniques of imunoinhibition used in the emergency room laboratories, what it constitute a serious problem in the diagnosis of squares of myocardial ischemia. The ignorance of this clinical situation has pushed us to present this study in order to begin to consider their utility like marker of illness, giving shortly, some recommendations for the correct management of this discovery in the emergency. SUBJECTS AND METHOD: They have been studied the total of patients valued in the emergency for 16 months that they gathered this requirements (25), valuing the pathology that appeared under this analytic determination. The identification of the isoenzymes of CK was carried out by means of agarose gel electrophoresis. RESULTS: The 13 cases with Macro-CK type I (9 women and 4 males) had a half age of 64 years (4-89). The levels means of CK were 274 mU/mL with a CK-MB of 440 U/L (166%). The 7 cases with Macro-CK type II (1 woman and 6 males) had a half age of 69 years (32-80). The levels means of CK were 314 mU/mL with a CK-MB of 569 U/L (191%). The 53.8% of the patients with Macro-CK type I presented any cardiovascular pathology, the 38.5% diabetes mellitus and the 30.8% pathology muscle-articulate with possible component autoimmune. The 100% of the patients with Macro-CK type II suffered processes malignant tumors, highlighting the presence of tumors of digestive origin and prostatic, with metastasis, being the more frequent in liver and bone (71.4%), and a high mortality of the 71.4% (5 deaths). The Macro-CK type II (form oligomer of mitochondrial) is liberated like consequence of a lesion of the mitochondrias of the affected fabrics tissues, associating to serious illnesses like cirrhosis and tumors. CONCLUSIONS: In all the studied cases the payees of Macro-CK presented underlying pathology, being in the case of Macro-CK type I of heart prevalence, and in the case of type II of nature tumoral. A management Macro-CK algorithm is also presented for the emergency.

Adolescent↗

PubMed2001

Coronary restenosis elimination with a sirolimus eluting stent: first European human experience with 6-month angiographic and intravascular ultrasonic follow-up.

AIMS: Coronary stenting is limited by a 10%-60% restenosis rate due to neointimal hyperplasia. Sirolimus is a macrocyclic lactone agent that interacts with cell-cycle regulating proteins and inhibits cell division between phases G1 and S1. The hypothesis tested in this study is that local delivery of sirolimus with an eluting stent can prevent restenosis. METHODS AND RESULTS: Fifteen patients were treated with 18 mm sirolimus eluting BX VELOCITY stents. Quantitative angiography and three-dimensional quantitative intravascular ultrasound were performed at implantation and at the 6 months follow-up. All stent implantations were successful. One patient died on day 2, of cerebral haemorrhage and one patient suffered a subacute stent occlusion due to edge dissection (re-PTCA, CKMB 42). At 9 months no further adverse events had occurred and all patients were angina free. Quantitative coronary angiography revealed no change in minimal lumen diameter and percent diameter stenosis and hence no in-lesion or in-stent restenosis. Quantitative intravascular ultrasound showed that intimal hyperplasia volume and percent obstruction volume at follow-up were negligible at 5.3 mm(3)and 1.8%, respectively. No edge effect was observed in the segments proximal and distal to the stents. CONCLUSION: Implantation of a sirolimus-eluting stent seems to effectively prevent intimal hyperplasia.

Adult↗

PubMedDate not supplied

Iodinated contrast agents. Effect on ATP: creatine N-phosphotransferase isoenzymes in arterial wall.

In the arterial wall, ATP:creatine N-phosphotransferase (E.C.2.7.3.2) is present in the form of its three isoenzymes, MM, MB, and BB, the latter being predominant. Six iodinated contrast agents in routine angiographic use were examined from the point of view of their effects in vitro on the isoenzymes of ATP:creatine N-phosphotransferase from the arterial wall, compared with their effects on the same isoenzymes in other organs. There is a clear inhibitory effect from the contrast agents on all organs, but it is least marked for the arterial wall. Furthermore, nonionic compounds have far less enzyme-inhibitory effect than ionic compounds.

Animals↗

PubMed1991

Longevity of adult ventricular rat heart muscle cells in serum-free primary culture.

The study had two aims: first, to improve the longevity of isolated adult cardiomyocytes in serum-free culture, and, second, to investigate whether catecholamines which promote hypertrophy in vivo can prolong survival of isolated adult rat cardiomyocytes in serum-free culture. The basic cell culture medium consists of serum-free medium 199 with 10(-7) M insulin. In this medium 50% of the initially plated cardiomyocytes survive in elongated form for 2 days. Omission of glutamine and supplementation of the basic medium with 5 mM creatine, 2 mM carnitine and 5 mM taurine extends survival of elongated cells to 14 days. In supplemented medium, normal cell ATP content is maintained (27 nmol/mg protein after 15 days), but cells gradually atrophy and reduce their protein mass. The trophic effects of catecholamines (epinephrine, norepinephrine, phenylephrine; 10 microM, added on day 3 of culture) were investigated. After addition of catecholamines the cells spread. Spreading can be prevented by prazosin (10 microM) and phentolamine (10 microM) but not by propranolol (10 microM), indicating that spreading is stimulated via the alpha 1-adrenoreceptor. Cells also spread in the presence of the phorbol ester phorbol myristate acetate (10 microM). Catecholamines reduce the progressive cell atrophy and protein loss. With 10 microM phenylephrine, cellular ATP content remained constant at 27 nmol/mg protein until day 15. The results indicate that agents which stimulate protein kinase C (alpha 1-agonists, phorbol esters) stimulate cell spreading, protein synthesis and long-term survival of cardiomyocytes in vitro.

Animals↗

PubMed2001

Impaired myofibrillar energetics and oxidative injury during human atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) is associated with severe contractile dysfunction and structural and electrophysiological remodeling. Mechanisms responsible for impaired contractility are undefined, and current therapies do not address this dysfunction. We have found that myofibrillar creatine kinase (MM-CK), an important controller of myocyte contractility, is highly sensitive to oxidative injury, and we hypothesized that increased oxidative stress and energetic impairment during AF could contribute to contractile dysfunction. Methods and Results-- Right atrial appendages were obtained from AF patients undergoing the Maze procedure and from control patients who were in normal sinus rhythm and undergoing cardiac surgery. MM-CK activity was reduced in AF patients compared with controls (25.4+/-3.4 versus 18.2+/-3.8 micromol/mg of myofibrillar protein per minute; control versus AF; P<0.05). No reduction in total CK activity or myosin ATPase activity was detected. This selective reduction in MM-CK activity was associated with increased relative expression of the beta-myosin isoform (25+/-6 versus 63+/-5%beta, CTRL versus AF; P<0.05). Western blotting of AF myofibrillar isolates demonstrated no changes in protein composition but showed increased prevalence of protein oxidation as detected by Western blotting for 3-nitrotyrosine (peroxynitrite biomarker) and protein carbonyls (hydroxyl radical biomarker; P<0.05). Patterns of these oxidative markers were distinct, which suggests discrete chemical events and differential protein vulnerabilities in vivo. MM-CK inhibition was statistically correlated to extent of nitration (P<0.01) but not to carbonyl presence. CONCLUSIONS: The present results provide novel evidence of oxidative damage in human AF that altered myofibrillar energetics may contribute to atrial contractile dysfunction and that protein nitration may be an important participant in this condition.

Aged↗

PubMed1994

Evaluation of creatine analogues as a new class of anticancer agents using freshly explanted human tumor cells.

BACKGROUND: The creatine kinase (CK) isozymes and their substrates, creatine and creatine phosphate, are believed to play a pivotal role in energy transduction in tissues with large, fluctuating energy demands, such as skeletal muscle, heart, and brain. This enzyme system may also be involved in the process of cellular transformation. Inhibition of tumor cell growth by creatine analogues has been observed and may be due to the ability of these analogues to impair cellular energy generation and utilization. PURPOSE: An in vitro human tumor colony-forming assay was used to predict the clinical usefulness of creatine analogues as anticancer agents. METHODS: The ability of cyclocreatine (1-carboxymethyl-2-iminoimidazolidine) and homocyclocreatine (1-carboxyethyl-2-iminoimidazolidine) to inhibit the growth of cells prepared from tumor samples taken directly from patients was evaluated by quantitative measurement of colony formation in a soft-agar cell culture assay system. Cyclocreatine was tested in this human tumor colony-forming assay at concentrations ranging from 0.067 to 20 mM against 128 tumor samples, 51 of which formed colonies in the assay and were considered evaluable. Homocyclocreatine was similarly tested at concentrations from 0.2 to 20 mM against 139 tumor samples; 54 were considered evaluable. The colony-forming assay was also used to compare the efficacy of the creatine analogues to representatives from the six major classes of standard chemotherapeutics (alkylating agents, antimetabolites, DNA intercalators, platinum compounds, topoisomerase inhibitors, and tubulin-interacting agents). In addition, CK levels were measured in 192 tumor samples that were taken from 166 patients. RESULTS: Cyclocreatine and homocyclocreatine, at concentrations previously achieved in animal tissues (7-20 mM), had antitumor activity against 19% and 50%, respectively, of tumor samples that formed colonies in the assay. Cyclocreatine was effective against a subset of tumors sensitive to homocyclocreatine (P = .023; Fisher's exact test), which was the more potent creatine analogue in this assay (P < .001; McNemar's test). No relationships were seen between tumor samples sensitive to the creatine analogues and those sensitive to standard chemotherapeutics. Pairwise Wilcoxon rank sum tests indicated that CK activity was significantly higher in tumors with any growth in the colony assay compared with tumors that did not grow (P < .025). CONCLUSIONS: The creatine analogues, cyclocreatine and homocyclocreatine, effectively reduced colony formation of freshly explanted human tumor cells. The mechanism of action or resistance to these compounds seems to differ from those of standard chemotherapeutics. IMPLICATIONS: Creatine analogues that may alter the energy status of the tumor cell potentially represent promising new anticancer agents that function through a unique mechanism.

Antineoplastic Agents↗

PubMed1999

Differential coupling of smooth and skeletal muscle pyruvate kinase to creatine kinase.

The interaction of pyruvate kinase from skeletal (SKPK) and smooth (SMPK) muscle with MM-creatine kinase (MMCK) and BB-creatine kinase (BBCK) was assessed using temporal absorbance changes, variations in absorbance at different wavelengths, concentration dependence, association in an electric field, and PK kinetic activity. SKPK exhibits a time course of absorbance increase in the presence of MMCK with a time constant of 29.5 min. This increase occurs at all wavelength from 240 to 1000 nm. At 195 nm, the combination of SKPK and MMCK produces a decrease in absorption with electric fields of both 0 and 204 V/cm. The change in SKPK-MMCK is saturable. SKPK activity is significantly increased by the presence of MMCK in solutions of 0-32% ethanol. These results indicate specific SKPK-MMCK interaction. SMPK and BBCK did not exhibit similar coupling when the BBCK concentration dependence of absorbance or SMPK activity in solutions of 0-32% ethanol was determined. Both MMCK and BBCK increased SKPK activity; neither MMCK nor BBCK increased SMPK activity. The ability to form diazymatic complexes with creatine kinase appears to reside in SKPK. This coupling may account for the increased flux through PK without significant substrate changes seen during skeletal muscle activation. This coupling will not occur in smooth muscle.

Animals↗

PubMed1976

Physicochemical studies on the creatine kinase M-line protein and its interaction with myosin and myosin fragments.

The M-line protein which is identical to the muscle form of creatine kinase was purified from rabbit skeletal muscle using ion exchange chromatography. Gel electrophoresis in the presence and absence of sodium dodecyl sulfate revealed the protein to be homogeneous. Sodium dodecyl sulfate gel electrophoresis gave 44 000 +/- 2000 as the minimum molecular weight while low speed sedimentation equilibrium experiments yielded a molecular weight of 84 000 +/- 4000, suggesting that the parent molecule is a dimer. Circular dichroism spectra revealed the presence of two negative dichroic bands located at 218 and 208 nm suggesting the presence of some beta-structure. Ellipticity values at these two wavelengths were -8000 +/- 400 and -9000 +/- 400 deg-cm2-dmol-1. Circular dichroism measurements indicated the protein to interact with myosin, heavy meromyosin and heavy meromyosin subfragment 1 (S1). The Ca2+-activated ATPase activities of myosin, heavy meromyosin and subfragment 1 were inhibited by the addition of M-line protein. When the protein was mixed with subfragment 1 in a 1:1 mole ratio in 0.15 M KC1, 50 mM Tris pH 8, low speed sedimentation equilibrium studies gave a molecular weight of 205 000 +/- 10 000 for the complex, indicative of an interaction of the two components. Both circular dichroism and sedimentation equilibrium studies indicated no interaction of M-line protein with light meromyosin.

Amino Acids↗

PubMed2004

Reduction of systolic and diastolic dysfunction by retrograde coronary sinus perfusion during off-pump coronary surgery.

OBJECTIVES: We evaluated the protective effects of retrograde coronary sinus perfusion to offset potential systolic and diastolic dysfunction (myocardial stunning) after temporary regional ischemia needed for off-pump coronary artery bypass grafting. METHODS: Twenty Yorkshire-Duroc pigs (31.8 +/- 3.9 kg) underwent 15 minutes of mid-left anterior descending coronary artery ischemia in the beating heart. In 8 pigs, no protective measures were used. In 12 pigs, an aorta-coronary sinus shunt (with conventional cannulas) allowed retrograde perfusion during temporary ischemia; in 6 of these pigs, no leakage to the right atrium was ensured. Regional endocardial contraction was measured with sonomicrometer crystals. Systolic dysfunction (impaired regional shortening), diastolic dysfunction (contraction extending into early diastole), and coronary sinus nitric oxide and endothelin-1 levels were recorded. RESULTS: Before ischemia, contraction did not extend into the diastolic interval. During ischemia, paradoxic bulging occurred in all hearts except in the occlusive coronary sinus shunt group (16% +/- 6% of baseline, P <.01). Sixty minutes after ischemia, systolic segment shortening recovered 36% +/- 24% without retrograde perfusion versus 56% +/- 20% and 61% +/- 14% with coronary sinus shunting (P <.05). Diastolic dysfunction (as percentage of diastolic time in contraction) was 38% +/- 16% in the nontreated group versus 22% +/- 22% and 9% +/- 9% (P <.05) after shunting and occlusive shunting, respectively. This correlated with a left ventricular end-diastolic pressure increase of 4 mm Hg in the ischemic group versus no change in the retrograde perfusion groups. Nitric oxide decreased 15% without shunting and increased 8% after occlusive coronary sinus shunting (P <.05). CONCLUSIONS: Retrograde coronary sinus perfusion during simulated off-pump coronary revascularization diminishes systolic and diastolic dysfunction. An aortic-coronary sinus shunt is a rapid, recognized approach that can improve myocardial muscle and endothelial safety during off-pump coronary artery bypass grafting.

Animals↗

PubMed1980

Phosphocretine production coupled to the glycolytic reactions in the cytosol of cardiac cells.

Phosphocreatine production ctalyzed by a cytosolic fraction from cardiac muscle containing all glycolytic enzymes and creatine kinase in a soluble form has been studied in the presence of creatine, adenine nucleotides and different glycolytic intermedites as substrates. Glycolytic depletion of glucose, fructose 1,6bis(phosphate) and phosphoenolpyruvate to lactte was coupled to efficient phosphocreatine production. The molar ratio of phosphocreatine to lactate produced was close to 2.0 when fructose 1,6bis(phosphate) was used as substrate and 1.0 with phosphoenolpyruvate. In these processes the creatine kinase reaction was not the rate-limiting step: themass action ratio of the creatine kinase reaction was very close to its equilibrium value and the maximal rate of the forward creatine kinase reaction exceeded that of glycolytic flux by about 6-fold when fructose 1,6-bis(phosphate) was used as a substrate. Therefore, the creatine kinase raction was continuously in the state of quasi-equilibrium and the efficient syntheses of phosphocreatine observed is a result of constant removal of ADP by the glycolytic system at an almost unchanged level of ATP ([ATP]>>[ADP]), this leading to a continuous shift of the creatine kinase equilibrium position. When phosphocreatine was added initially at concentrations of 5---15 mM the rate of the coupled creatine kinase and glycolytic reactions was very significantly inhibited due to a sharp decrease in the steady-state concentration of ADP. Therefore, under conditions of effective phosphocreatine production in heart mitochondria, which maintain a high phosphocreatine: creatine ratio in the myoplasm in vivo, the glycolytic flux may be suppressed due to limited availability of ADP restricted by the creatine kinase system. The possible physiological role of the control of the glycolytic flux by the creatine kinase system is discussed.

Creatine Kinase↗

PubMed1997

Preconditioning improves myocardial preservation in patients undergoing open heart operations.

BACKGROUND: Our previous work has shown that preconditioning can promote the recovery of cardiac function in patients having an open heart procedure. Because preconditioning is regarded as the most powerful form of endogenous myocardial protection, we tested the hypothesis that preconditioning protects against myocardial ischemia-reperfusion injury in patients undergoing prolonged cold crystalloid cardioplegic arrest. METHODS: Thirty patients who had rheumatic heart disease and required both aortic and mitral valve replacement were studied. Patients were randomly divided into two equal groups. Preconditioning was accomplished using two cycles of 2-minute occlusion of the vena cava and aorta followed by 3 minutes of reperfusion under cardiopulmonary bypass. All hearts were arrested with 4 degrees C St. Thomas' Hospital cardioplegic solution. Myocardial protective effects were assessed by changes in myocardial levels of adenosine triphosphate, electrocardiographic activity, leakage of myocardial enzymes, and myocardial contractility. RESULTS: The adenosine triphosphate content in ischemic myocardium was higher in the preconditioning group than in the control group (p < 0.05 90 minutes after ischemia), and there was a significant reduction in release of the myocardial-specific isoenzyme of creatine kinase in the preconditioning group. Preconditioning improved the recovery of myocardial contractility (first derivative of left ventricular developed pressure, 1,490 +/- 102 mm Hg/s versus 1,250 +/- 97 mm Hg/s 30 minutes after reperfusion; p < 0.05), and there was also a protective effect on electrocardiographic activity. CONCLUSIONS: Our results suggest that ischemic preconditioning protects the myocardium in humans from the severe ischemia-reperfusion injury produced after prolonged arrest with cold crystalloid cardioplegia.

Adenosine Triphosphate↗

PubMed2004

High molecular mass kininogen inhibits metalloproteinases of Bothrops jararaca snake venom.

High molecular mass kininogen (HK) purified from Bothrops jararaca (Bj) plasma was tested on activities of the Bj venom in vivo and in vitro. Results showed that, when incubated with BjHK, the Bj venom presented inhibition on hemorrhagic, edema forming, myotoxic, and coagulant activities. It is well known that metalloproteinases are directly or indirectly involved in these activities. Similarly, human HK inhibits the hemorrhagic effect of the Bj venom as well as hemorrhagic and enzymatic effects of jararhagin, a hemorrhagic metalloproteinase isolated from Bj venom. Complex between HK and jararhagin was not detected by gel filtration. Nevertheless, the inhibitory effect of the hemorrhagic activity of the venom was only partial when HK was pre-incubated with 0.4mM ZnCl(2) or with 0.45mM CaCl(2). These data suggest that the inhibitory effect depends, at least partially, on the competition for ions between kininogen and metalloproteinases of the venom.

Animals↗

PubMed2002

A preservation solution with polyethylene glycol and calcium: a possible multiorgan liquid.

The addition of polyethylene glycol (PEG) to hepatocyte storage medium is known to decrease lipid peroxidation and swelling and to protect the cell cytoskeleton from cold. We therefore decided to investigate the effect of substituting PEG for hydroxyethyl starch (HES) in an extracellular-like UW solution, with and without Ca++, on rat liver preservation. Isolated perfused rat livers were used to assess graft injury after 24h of cold storage. Four groups of preserved livers ( n=6 for each group) were compared to controls (non preserved livers, n=11). For this purpose, Belzer solution (K+-UW, group 1) was stepwise modified. Group 2 (Na+-UW) was treated with the same liquid, however with inverted concentrations of Na+ and K+. Group 3 was preserved in the first experimental solution (EPS-1) with Ca++ (0.5mM) added to the Na+-UW solution. In the EPS-2 (group 4), PEG-35 (0.03mM) was substituted for HES. The last group, EPS-3 (group 5) was treated with the same compounds as EPS-2, but without Ca++. After 24h of cold storage and 120min normothermic reperfusion, there was no statistical difference in transaminases (ALT and AST) release between the control and the Na+-UW groups. Furthermore, rat livers preserved in Na+-UW solution released less ( P<0.05) ALT and AST and excreted more ( P<0.05) indocyanine green (ICG) than livers preserved in K+-UW solution. The addition of 0.5mM Ca++ to Na+-UW solution (EPS-1) dramatically increased ( P<0.05) parenchymal (ALT, AST) and non parenchymal (creatine kinase-BB) cellular injury. The substitution of PEG (0.03mM) for HES (EPS-2) reduced ( P<0.05) membrane injuries due to Ca++ while bile flow was statistically increased ( P<0.05). Finally, the omission of Ca++ from EPS-2, that is EPS-3, has no statistically significant effect on the studied parameters. PEG effectively protected the rat liver grafts from the onset of hypothermic ischemia-reperfusion and Ca++ damages and thus may be a valuable additive to preservation solutions.

Animals↗

PubMed1998

Percutaneous transluminal septal myocardial ablation in hypertrophic obstructive cardiomyopathy: results with respect to intraprocedural myocardial contrast echocardiography.

BACKGROUND: Percutaneous transluminal septal myocardial ablation (PTSMA) has been introduced as an alternative procedure for reducing the left ventricular outflow tract gradient (LVOTG) in hypertrophic obstructive cardiomyopathy. We report on the acute and mid-term results in 91 symptomatic patients with respect to intraprocedural myocardial contrast echocardiography (MCE). METHODS AND RESULTS: PTSMA was intended for 46 women and 45 men (54.1+/-15.5 years). In 2 patients, the intervention could not be completed. In the first 30 patients the target vessel was determined by probatory balloon occlusion alone and in the remainder by additional intraprocedural MCE. Resting LVOTG was reduced from 73.8+/-35.4 to 16.6+/-18.1 and nostextrasystolic LVOTG from 149.3+/-42.5 to 61. 9+/-43.0 mm Hg (P<0.0001 each). In 10 (11%) patients, permanent DDD pacemaker implantation was necessary. Two (2%) patients died, 1 from ventricular fibrillation associated with treatment for chronic obstructive pulmonary disease after 9 days and 1 from fulminant pulmonary embolism after 2 days. After 3 months, mean New York Heart Association class was reduced from 2.8+/-0.6 to 1.1+/-1.0 (P<0.0001). The LVOTG remained reduced to 14.6+/-25.5 mm Hg at rest and 49. 1+/-48.7 mm Hg (P<0.0001 each). Four patients underwent successful repeat PTSMA. Determination of the target vessel by MCE was associated with a higher rate of acute (92% vs 70%; P<0.01) and mid-term (94% vs 64%; P<0.01) success. CONCLUSIONS: PTSMA is a promising nonsurgical technique for reduction of symptoms and LVOTG in hypertrophic obstructive cardiomyopathy. MCE has been shown to be a useful addition to probatory balloon occlusion for target vessel selection. Prospective, long-term observations of larger populations and a comparison with the established forms of therapy are necessary to determine the definitive significance of PTSMA.

Adolescent↗