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2.
Heart ; 95(19): 1572-8, 2009 Oct.
Article in English | MEDLINE | ID: mdl-19482849

ABSTRACT

BACKGROUND: A bimodal distribution of measures of restenosis has been demonstrated at 6-8 months after bare metal stent implantation. Drug-eluting stent (DES) treatment has attenuated the impact of certain factors (eg, diabetes) on restenosis but its effect on the distribution of indices of restenosis is not known. OBJECTIVE: To perform a detailed analysis of the metrics of restenosis indices after DES implantation. Design, settings, PATIENTS: Prospective observational study of patients undergoing DES implantation (Cypher, sirolimus-eluting stent; or Taxus, paclitaxel-eluting stent) at two German centres, with repeat angiography scheduled at 6-8 months after coronary stenting. MAIN OUTCOME MEASURES: In-stent late luminal loss (LLL) and in-segment percentage diameter stenosis (%DS) as determined by quantitative coronary angiography at recatheterisation. RESULTS: Paired cineangiograms were available for 2057 patients. Overall mean (SD) LLL was 0.31 (0.50) mm; mean (SD) %DS was 30.3 (15.7)%. Distribution of both LLL and %DS differed significantly from normal (Kolmogorov-Smirnov test; p<0.001 for each). For both parameters a mixed distribution model better described the data (likelihood ratio test with 3df; p<0.001 for each). This consisted of two normally distributed subpopulations with means (SD) of 0.10 (0.25) mm and 0.69 (0.60) mm for LLL, and means (SD) of 22.2 (8.6)% and 40.1 (16.6)% for %DS. The results were consistent across subgroups of DES type, "on-label" versus "off-label" indication, and presence or absence of diabetes. CONCLUSIONS: LLL and %DS at follow-up angiography after DES implantation have a complex mixed distribution that may be accurately represented by a bimodal distribution model. The introduction of DES treatment has not resulted in elimination of a variable propensity to restenosis among subpopulations of patients with stented lesions.


Subject(s)
Coronary Restenosis/diagnostic imaging , Drug-Eluting Stents , Aged , Blood Vessel Prosthesis , Chi-Square Distribution , Coronary Angiography/statistics & numerical data , Coronary Restenosis/pathology , Drug-Eluting Stents/statistics & numerical data , Female , Humans , Male , Myocardial Ischemia/therapy , Paclitaxel/administration & dosage , Prospective Studies , Prosthesis Failure , Sirolimus/administration & dosage , Treatment Outcome , Tubulin Modulators/administration & dosage
3.
Heart ; 95(2): 107-12, 2009 Feb.
Article in English | MEDLINE | ID: mdl-18801777

ABSTRACT

OBJECTIVE: To assess the prognostic value of the baseline C-reactive protein (CRP) level in patients undergoing percutaneous coronary intervention (PCI) after pre-treatment with 600 mg of clopidogrel and whether there is an interaction between CRP level and abciximab in terms of outcome. DESIGN: Pooled analysis from the ISAR-SWEET, SMART-2, ISAR-REACT and REACT-2 trials. SETTING, METHODS: The study included 4847 patients with coronary artery disease (CAD) undergoing PCI after pre-treatment with 600 mg of clopidogrel. The primary outcome was one-year mortality. The combined incidence of death, myocardial infarction and target lesion revascularisation was the secondary outcome. RESULTS: Based on the median value of CRP (2.3 mg/l), patients were divided into two groups: the high-CRP group (n = 2448) and the low-CRP group (n = 2399). During one year, there were 141 deaths (5.8%) in the high-CRP group compared with 51 deaths (2.1%) in the low-CRP group (OR = 2.77, 95% CI 2.04 to 3.77; p<0.001). The incidence of major adverse cardiac events (MACE) was 28% in the high-CRP group compared with 25% in the low-CRP group (OR = 1.13, 95% CI 1.01 to 1.26; p = 0.034). The Cox proportional hazards model showed that high CRP was an independent predictor of one-year mortality (hazard ratio 2.20, 95% CI 1.54 to 3.15; p<0.001 for CRP level >2.3 mg/l vs CRP level < or =2.3 mg/l). No significant interaction was observed between CRP level and abciximab regarding one-year mortality (p = 0.08) or MACE (p = 0.68). CONCLUSION: In patients with CAD undergoing PCI after pretreatment with 600 mg of clopidogrel, baseline CRP level predicts one-year mortality and MACE. Abciximab therapy did not confer any particular beneficial effect in patients with a higher inflammatory burden.


Subject(s)
Angioplasty, Balloon, Coronary , Antibodies, Monoclonal/therapeutic use , C-Reactive Protein/metabolism , Coronary Disease/therapy , Immunoglobulin Fab Fragments/therapeutic use , Platelet Aggregation Inhibitors/therapeutic use , Ticlopidine/analogs & derivatives , Abciximab , Aged , Biomarkers/blood , Clopidogrel , Coronary Disease/mortality , Female , Humans , Male , Multicenter Studies as Topic , Myocardial Infarction/mortality , Myocardial Infarction/prevention & control , Preoperative Care , Prognosis , Randomized Controlled Trials as Topic , Ticlopidine/therapeutic use
4.
Minerva Cardioangiol ; 56(5): 493-510, 2008 Oct.
Article in English | MEDLINE | ID: mdl-18813185

ABSTRACT

Since its inception in the 1960s, coronary revascularization has established itself as a fundamental therapy for treating the acute and chronic manifestations of atherosclerotic coronary disease. Catheter-based techniques were realized in the late 1970s and have evolved from balloon dilatation of simple, discrete stenoses to complex, multivessel interventions across the spectrum of coronary disease presentations. In retrospect, there were two defining technological developments the introduction of coronary stenting which enabled more stable acute outcomes and the evolution of drug-eluting stents which ameliorated the effect of neointimal hyperplasia the dominant cause of delayed loss of efficacy. The role of catheter-based intervention in multivessel disease is well established in the treatment of ST-elevation myocardial infarction and acute coronary syndromes. On the contrary, in the arena of in stable coronary disease, its utility is keenly debated. The pace of development in cardiovascular pharmacology has rendered early investigation of best treatment strategies largely obsolete, while newer revascularization techniques have successfully extended the remit of catheter-based multivessel intervention strategies to include left main stem disease, bifurcation stenosis and chronic occlusions. Consequently complete revascularization is now available via a percutaneous approach and conventional beliefs relating to choice of revascularization strategy deserve re-assessment. The authors present a contemporary review of the literature and a challenge against fallacies in its interpretation.


Subject(s)
Angioplasty, Balloon, Coronary , Coronary Artery Bypass , Coronary Artery Disease/surgery , Diabetes Complications/surgery , Humans
5.
J Intern Med ; 264(5): 472-80, 2008 Nov.
Article in English | MEDLINE | ID: mdl-18624903

ABSTRACT

OBJECTIVES: Optimal antithrombotic/anticoagulation therapy in patients on chronic oral anticoagulation (OAC) undergoing drug-eluting stent (DES) implantation is unknown. We investigated the efficacy and safety of two regimens of antithrombotic/anticoagulation therapy in patients who present for DES implantation whilst on OAC. METHODS: We included a series of 515 patients on OAC who underwent DES implantation between 2002 and 2007. Based on predefined clinical and echocardiographic criteria, 306 patients continued OAC (triple therapy) and 209 patients discontinued OAC (dual therapy) for the time they received antiplatelet therapy with clopidogrel and aspirin [stent-related antithrombotic treatment (SRAT)]. The primary end point was a composite of death, myocardial infarction, stent thrombosis or stroke. RESULTS: During SRAT the primary endpoint was observed in 13 patients in the group with triple therapy versus 15 patients in the group with dual therapy [Kaplan-Meier estimates 4.2% and 7.2%, odds ratio (OR) = 0.61, 95% confidence interval (CI) 0.29-1.28; P = 0.19]. At 2 years of follow-up, the primary endpoint was observed in 35 patients in the group with triple therapy versus 36 patients in the group with dual therapy (Kaplan-Meier estimates 14.1% and 18.0%, OR = 0.76, 95% CI: 0.48-1.21; P = 0.25). Two-year incidence of major bleeding was 1.4% (n = 4, triple therapy) versus 3.1% (n = 6, dual therapy) (P = 0.34). CONCLUSIONS: In patients on chronic OAC undergoing DES implantation, clinical and echocardiographic criteria help to define postprocedural antithrombotic/anticoagulation therapy. Based on these criteria, both a double antiplatelet therapy (clopidogrel plus aspirin) and a triple therapy (OAC plus clopidogrel plus aspirin) are associated with favourable safety and efficacy.


Subject(s)
Anticoagulants/therapeutic use , Aspirin/administration & dosage , Drug-Eluting Stents , Phenprocoumon/administration & dosage , Platelet Aggregation Inhibitors/therapeutic use , Ticlopidine/analogs & derivatives , Aged , Aspirin/therapeutic use , Clopidogrel , Coronary Vessels/surgery , Drug Therapy, Combination , Female , Follow-Up Studies , Humans , Kaplan-Meier Estimate , Male , Phenprocoumon/therapeutic use , Postoperative Period , Prospective Studies , Stroke/mortality , Stroke/prevention & control , Ticlopidine/administration & dosage , Ticlopidine/therapeutic use , Treatment Outcome
6.
Minerva Cardioangiol ; 54(5): 539-55, 2006 Oct.
Article in English | MEDLINE | ID: mdl-17019392

ABSTRACT

Percutaneous coronary interventions with the use of stents have become the mainstay treatment of patients with various clinical manifestations of coronary artery disease. Despite their remarkable success, restenosis has remained the major drawback and its prevention has absorbed intensive experimental and clinical research work. After the failure of multiple efforts with systemic use of various drugs, local application of antiproliferative and anti-inflammatory agents released by specially designed coated stents led to considerable suppression of neointima and opened new prospects in the prevention of restenosis. An increasing body of evidence is showing the advantages provided by drug-eluting stents (DES) in almost all subsets of patients with coronary artery disease with a drastic decrease in the need for reintervention. To date, the most commonly used and the only US Food and Drug Administration (FDA) approved DES are a sirolimus-eluting stent (Cypher) and a paclitaxel-eluting stent (Taxus), both of which are polymer-based DES and will constitute the focus of this review. Recent data demonstrate that DES are not equal in their safety and efficacy. A less optimistic aspect of DES technology are the reiterated concerns about a more prolonged risk of stent thrombosis. Although all agree on the need of a longer duration of dual antiplatelet therapy in patients treated with DES, its optimal length is still to be defined. Because polymers used for stent coating are often seen at the origin of the compromised long-term safety of DES, new technologies able to avoid permanent polymers may offer a valuable alternative.


Subject(s)
Coronary Artery Disease/therapy , Drug Delivery Systems , Immunosuppressive Agents/administration & dosage , Paclitaxel/administration & dosage , Sirolimus/administration & dosage , Stents , Tubulin Modulators/administration & dosage , Combined Modality Therapy , Humans , Polymers , Prosthesis Design , Randomized Controlled Trials as Topic
8.
Catheter Cardiovasc Interv ; 53(2): 248-52, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11387615

ABSTRACT

We describe a case of isolated right ventricular infarction that has rarely been diagnosed antemortem. Electrocardiogram showed ST segment elevation in left precordial chest, right precordial chest, and inferior leads, which mimicked those of anterior and inferior left ventricular infarction. Coronary angiography revealed that culprit lesion was totally occluded right coronary artery. Infarcted artery was nondominant right coronary artery with branches supplying only right ventricular wall. Restoration of coronary blood flow was obtained by primary stenting and resulted in prompt ST segment normalization in all leads. Despite extensive right ventricular wall motion abnormality, subsequent right ventricular dysfunction was not observed.


Subject(s)
Angioplasty , Myocardial Infarction/surgery , Ventricular Dysfunction, Right/surgery , Aged , Humans , Male
9.
J Immunol ; 166(11): 6578-84, 2001 Jun 01.
Article in English | MEDLINE | ID: mdl-11359810

ABSTRACT

The role of mouse liver NK1.1 Ag(+) T (NKT) cells in the antitumor effect of alpha-galactosylceramide (alpha-GalCer) has been unclear. We now show that, whereas alpha-GalCer increased the serum IFN-gamma concentration and alanine aminotransferase activity in NK cell-depleted C57BL/6 (B6) mice and B6-beige/beige mice similarly to its effects in control B6 mice, its enhancement of the antitumor cytotoxicity of liver mononuclear cells (MNCs) was abrogated. Depletion of both NK and NKT cells in B6 mice reduced all these effects of alpha-GALCER: Injection of Abs to IFN-gamma also inhibited the alpha-GalCer-induced increase in antitumor cytotoxicity of MNCS: alpha-GalCer induced the expression of Fas ligand on NKT cells in the liver of B6 mice. Whereas alpha-GalCer did not increase serum alanine aminotransferase activity in B6-lpr/lpr mice and B6-gld/gld mice, it increased the antitumor cytotoxicity of liver MNCS: The alpha-GalCer-induced increase in survival rate apparent in B6 mice injected intrasplenically with B16 tumor cells was abrogated in beige/beige mice, NK cell-depleted B6 mice, and B6 mice treated with Abs to IFN-gamma. Depletion of CD8(+) T cells did not affect the alpha-GalCer-induced antitumor cytotoxicity of liver MNCs but reduced the effect of alpha-GalCer on the survival of B6 mice. Thus, IFN-gamma produced by alpha-GalCer-activated NKT cells increases both the innate antitumor cytotoxicity of NK cells and the adaptive antitumor response of CD8(+) T cells, with consequent inhibition of tumor metastasis to the liver. Moreover, NKT cells mediate alpha-GalCer-induced hepatocyte injury through Fas-Fas ligand signaling.


Subject(s)
Antineoplastic Agents/administration & dosage , Galactosylceramides/administration & dosage , Hepatocytes/immunology , Hepatocytes/pathology , Liver Neoplasms, Experimental/prevention & control , Liver Neoplasms, Experimental/secondary , Alanine Transaminase/blood , Animals , Antibodies, Monoclonal/administration & dosage , Antigens/immunology , Antigens, Ly , Antigens, Surface , Antineoplastic Agents/antagonists & inhibitors , Antineoplastic Agents/toxicity , Cytotoxicity, Immunologic/genetics , Enzyme Activation/immunology , Fas Ligand Protein , G(M1) Ganglioside/immunology , Galactosylceramides/antagonists & inhibitors , Galactosylceramides/toxicity , Growth Inhibitors/administration & dosage , Growth Inhibitors/toxicity , Growth Substances/administration & dosage , Growth Substances/toxicity , Immune Sera/administration & dosage , Injections, Intralymphatic , Injections, Intravenous , Interferon-gamma/antagonists & inhibitors , Interferon-gamma/blood , Interferon-gamma/immunology , Killer Cells, Natural/immunology , Killer Cells, Natural/metabolism , Killer Cells, Natural/pathology , Lectins, C-Type , Leukocytes, Mononuclear/immunology , Ligands , Liver Neoplasms, Experimental/genetics , Liver Neoplasms, Experimental/pathology , Lymphocyte Count , Lymphocyte Depletion , Male , Melanoma, Experimental/immunology , Melanoma, Experimental/mortality , Membrane Glycoproteins/biosynthesis , Mice , Mice, Inbred C57BL , Mice, Inbred MRL lpr , Mice, Mutant Strains , NK Cell Lectin-Like Receptor Subfamily B , Proteins/immunology , Spleen , Survival Analysis , T-Lymphocyte Subsets/immunology , T-Lymphocyte Subsets/metabolism , T-Lymphocyte Subsets/pathology , Tumor Cells, Cultured/transplantation
11.
Oncol Res ; 12(2): 51-8, 2000.
Article in English | MEDLINE | ID: mdl-11132924

ABSTRACT

Liver metastasis of primary tumors is clinically a major problem. We examined the antitumor activity of KRN7000, an alpha-galactosylceramide, in mice with liver metastasis of the B16 melanoma. KRN7000 significantly inhibited tumor growth in the liver, and its potency was similar to that of interleukin-12. The KRN7000 administration resulted in a high percentage of cured mice, which acquired tumor-specific immunity. To study what kinds of antitumor effector cells participated in killing tumor cells, we then performed immunohistological analysis of tumor-infiltrating cells, and found that KRN7000 induced marked invasion of NK1.1+ cells, CD8+ cells, and F4/80+ cells (macrophages) into B16 tumor nodules. In addition, it appeared that KRN7000-treated, liver-associated macrophages possessed strong lytic activity against tumor cells. These results suggest that NK cells, NK1.1+ T (NKT) cells, cytotoxic T lymphocytes, and macrophages play an important role in killing tumor cells in the liver, and that KRN7000 may be useful for the treatment of cancer liver metastasis.


Subject(s)
Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Galactosylceramides/pharmacology , Galactosylceramides/therapeutic use , Melanoma, Experimental/drug therapy , Animals , Antigens/metabolism , Antigens, Differentiation/metabolism , Antigens, Ly , Antigens, Surface , CD8 Antigens/metabolism , Female , Immunohistochemistry , Interleukin-12/pharmacology , Lectins, C-Type , Liver Neoplasms/secondary , Macrophages/metabolism , Melanoma, Experimental/pathology , Mice , Mice, Inbred C57BL , NK Cell Lectin-Like Receptor Subfamily B , Neoplasm Metastasis , Neoplasm Transplantation , Proteins/metabolism , Recombinant Proteins/pharmacology , Time Factors , Tumor Cells, Cultured
12.
J Biochem ; 126(5): 912-6, 1999 Nov.
Article in English | MEDLINE | ID: mdl-10544285

ABSTRACT

We examined the effects of various protease inhibitors on Xenopus laevis embryogenesis. Aprotinin, a serine protease inhibitor, was found to inhibit embryogenesis markedly, but other protease inhibitors had virtually no effect. The inhibitory effect of aprotinin was specific for embryos at the blastula or gastrula stage. These results suggest that an aprotinin-sensitive protease involved in embryonic development is secreted from the embryos or appears on the surface of embryonic cells at these stages. We found that various serine proteases are in fact secreted from the embryos with their development and that some of them are sensitive to aprotinin.


Subject(s)
Aprotinin/pharmacology , Embryonic and Fetal Development/drug effects , Serine Proteinase Inhibitors/pharmacology , Xenopus laevis/embryology , Amino Acid Sequence , Animals , Blastocyst/drug effects , Culture Media , Embryonic and Fetal Development/physiology , Endopeptidases/metabolism , Gastrula/drug effects , Oligopeptides/chemistry , Protease Inhibitors/pharmacology , Serine Endopeptidases/physiology , Substrate Specificity , Time Factors , Xenopus laevis/physiology
13.
Cancer Res ; 58(6): 1202-7, 1998 Mar 15.
Article in English | MEDLINE | ID: mdl-9515806

ABSTRACT

Colorectal liver metastasis is clinically a major problem. We examined the antitumor activity of KRN7000, an alpha-galactosylceramide, on mice with liver metastases of adenocarcinoma Colon26 cells. KRN7000 treatment, beginning 1 day after tumor inoculation (day 1), significantly inhibited tumor growth in the liver, and its potency was equal to that of interleukin 12. KRN7000 treatment from day 3 caused regression of established Colon26 nodules. KRN7000 administration resulted in a high percentage of cured mice that acquired tumor-specific immunity. In addition, it appeared that highly activated, liver-associated natural killer cells made the major contribution to the killing of Colon26 cells in the liver. These results suggest that KRN7000 may be useful for the treatment of colorectal liver metastasis.


Subject(s)
Adenocarcinoma/drug therapy , Antineoplastic Agents/therapeutic use , Colorectal Neoplasms/drug therapy , Galactosylceramides/therapeutic use , Liver Neoplasms/secondary , Adjuvants, Immunologic/therapeutic use , Animals , Cytotoxicity, Immunologic , Dose-Response Relationship, Drug , Female , Interleukin-12/therapeutic use , Killer Cells, Natural/immunology , Leukocytes, Mononuclear/enzymology , Liver/immunology , Liver Neoplasms/immunology , Mice , Mice, Inbred BALB C , Neoplasms, Experimental/drug therapy
14.
Oncol Res ; 10(11-12): 561-8, 1998.
Article in English | MEDLINE | ID: mdl-10367937

ABSTRACT

Liver metastasis of primary tumor is a clinically major problem. KRN7000, an alpha-galactosylceramide, significantly augments natural killer (NK) activity of spleen cells and shows strong antitumor activity in mice with lung metastasis of melanoma B16 cells. To test whether KRN7000 has an antitumor activity in mice with hepatic metastasis of tumors, we examined the effect of KRN7000 on NK activity of hepatic mononuclear cells (MNC) and the antitumor activity in mice with liver metastasis of EL-4 cells. The in vivo administration of KRN7000 significantly augmented NK activity of hepatic MNC and inhibited tumor growth of EL-4 cells in the liver more markedly than chemotherapeutic agents, leading to a relatively high rate of cured mice. In addition, it appeared that the KRN7000 treatment is effective in mice with established EL-4 tumors. Moreover, we found that KRN7000 can produce significant amounts of interleukin 2 (IL-2), IL-4, IL-12, and interferon-gamma in a dose-dependent manner. These results suggest that KRN7000 will be useful for the treatment of cancer liver metastasis.


Subject(s)
Antineoplastic Agents/pharmacology , Cytokines/biosynthesis , Galactosylceramides/pharmacology , Liver Neoplasms, Experimental/drug therapy , Liver Neoplasms, Experimental/secondary , Animals , Female , Interferon-gamma/blood , Interleukin-12/blood , Interleukin-2/blood , Interleukin-4/blood , Liver Neoplasms, Experimental/metabolism , Lung Neoplasms/drug therapy , Lung Neoplasms/metabolism , Lung Neoplasms/secondary , Melanoma/drug therapy , Melanoma/metabolism , Melanoma/secondary , Mice
15.
Gan To Kagaku Ryoho ; 24(11): 1477-85, 1997 Sep.
Article in Japanese | MEDLINE | ID: mdl-9309145

ABSTRACT

We searched marine invertebrates for new host defence molecules. We found several new cytolytic factors in Arthropoda and Mollusca. Especially, sea hares were revealed to have strong antitumor glycoproteins. These novel glycoproteins were purified to apparent homogeneity from Aplysia kurodai and Dolabella auricularia, and designated aplysianins and dolabellanins, respectively. The isolated glycoproteins lysed all the tumor cells tested, including TNF-resistant cells, but did not lyse normal white and red blood cells. The glycoproteins completely inhibited the synthesis of DNA and RNA by tumor cells within 2 hours and caused tumor lysis within 18 hours. Cytolysis was inhibited by the presence of N-acetylneuraminic acid, suggesting that the recognition of the sugar moiety is a key step in the tumor lysis by these antineoplastic glycoproteins from sea hares. These antitumor factors, except dolabellanins C and P, also showed anti-microbial activities. The sequence of the N-terminal part of dolabellanin A was similar to aplysianin A and achacin.


Subject(s)
Antineoplastic Agents/isolation & purification , Arthropods/chemistry , Glycoproteins/isolation & purification , Mollusca/chemistry , Animals , Aplysia/chemistry , Glycoproteins/chemistry
16.
Pediatr Neurol ; 16(4): 319-22, 1997 May.
Article in English | MEDLINE | ID: mdl-9258966

ABSTRACT

It remains difficult to predict, early enough to intervene effectively, the risk of the development of learning disabilities among extremely low birth weight (ELBW) infants (birth weights less than 1,000 g). We prospectively studied the relationship between dilatations of lateral ventricles of the cranial computed tomography (CT) scan taken at the postconceptional age of 40 weeks and learning disabilities in their school age. Using a computer digitizer, we measured the areas of ventricles on cranial CT scans. The mean area of lateral ventricles of the learning disabilities-suspected group was significantly larger than that of the control group (392.9 and 277.4 mm2, respectively; P < .01). There were no significant differences between the two groups in gestation, birth weight, physical measurements, and developmental quotients at early school age. The dilatation of the lateral ventricles assessed by cranial CT at the corrected term may be one of the first predictors of learning disabilities recognizable at early school age.


Subject(s)
Brain/diagnostic imaging , Infant, Premature , Infant, Very Low Birth Weight , Learning Disabilities/diagnosis , Cerebral Ventriculography , Child , Humans , Infant, Newborn , Learning Disabilities/etiology , Predictive Value of Tests , Prospective Studies , Treatment Outcome
17.
Cardiovasc Res ; 33(3): 677-85, 1997 Mar.
Article in English | MEDLINE | ID: mdl-9093539

ABSTRACT

OBJECTIVE: The purpose of the present study was to examine the effects of preconditioning on glycolysis and oxidative phosphorylation during reperfusion in perfused rat hearts. METHODS: Preconditioning was induced by 5 min of ischemia and 5 min of reperfusion before 40 min of sustained ischemia and subsequent 30 min of reperfusion. Tissue energy metabolite levels, mitochondrial oxygen consumption capacity and adenine nucleotide translocator content of the perfused hearts were assessed at 40 min of ischemia, 5 and 30 min of reperfusion. RESULTS: Preconditioning improved the postischemic recovery of rate x pressure product (92.5 +/- 8.7 vs. 24.9 +/- 1.2% for non-preconditioned group) and high-energy phosphate content (ATP and CrP; 39.5 +/- 2.0 and 96.2 +/- 4.9% of initial vs. 24.1 +/- 0.9 and 56.1 +/- 4.3% of initial for the non-preconditioned group). The mitochondrial oxygen consumption capacity and the adenine nucleotide translocator content of the non-preconditioned heart were decreased by sustained ischemia and remained decreased throughout reperfusion. Preconditioning prevented these decreases. The tissue lactate level of the non-preconditioned heart was high throughout reperfusion (16.5-fold vs. basal), whereas in the preconditioned heart it returned to the basal level within a few minutes of reperfusion. Furthermore, the ratios of [fructose 1,6-bisphosphate]/([glucose 6-phosphate] + [fructose 6-phosphate]) at 5-min reperfusion were higher (2.2-fold) than those of the non-preconditioned heart. CONCLUSIONS: The results suggest that preconditioning preserves the capacity for normal mitochondrial function and the facilitation of glycolysis during reperfusion, which may play an important role in the improvement of postischemic contractile function and high-energy phosphate content.


Subject(s)
Ischemic Preconditioning, Myocardial , Mitochondria, Heart/physiology , Myocardial Ischemia/metabolism , Myocardial Reperfusion , Myocardium/metabolism , Adenosine Triphosphate/metabolism , Animals , Electron Transport Complex IV/metabolism , Fructosephosphates/metabolism , Glucosephosphates/metabolism , Glycolysis , Male , Mitochondria, Heart/drug effects , Mitochondria, Heart/metabolism , Mitochondrial ADP, ATP Translocases/metabolism , Oxygen Consumption , Rats , Rats, Sprague-Dawley , Saponins/pharmacology
18.
Dev Comp Immunol ; 19(1): 13-9, 1995.
Article in English | MEDLINE | ID: mdl-7615134

ABSTRACT

We observed for the first time that antifungal activity was exhibited by Aplysianin E (AKE), an antineoplastic and antibacterial glycoprotein purified from the eggs of Aplysia kurodai. AKE completely suppressed growth of the yeast form fungi, Saccharomyces cerevisiae A 5 8 1 A, Schizosaccharomyces pombe JY 1 and Candida albicans ATCC 36232 at a concentration of over 16 micrograms/mL. The colony-forming abilities of the fungi were also significantly decreased after contact with AKE. These results indicate that AKE has an antifungal property and that its mode of action is fungicidal.


Subject(s)
Anti-Bacterial Agents/pharmacology , Antibiotics, Antineoplastic/pharmacology , Antifungal Agents/pharmacology , Egg Proteins/pharmacology , Glycopeptides , Candida albicans/drug effects , Candida albicans/growth & development , Saccharomyces cerevisiae/drug effects , Saccharomyces cerevisiae/growth & development , Schizosaccharomyces/drug effects , Schizosaccharomyces/growth & development
19.
Biol Pharm Bull ; 17(8): 1144-6, 1994 Aug.
Article in English | MEDLINE | ID: mdl-7820128

ABSTRACT

Dolabellanin A (DAA), the antineoplastic and antibacterial glycoprotein purified from the albumen gland of Dolabella auricularia, showed an antifungal activity. DAA suppressed fungal growth completely at a concentration of over 2 micrograms/ml, and the colony forming ability of the fungus was significantly decreased after contact with DAA. These results indicate that DAA is an antifungal protein and its mode of antifungal activity is fungicidal.


Subject(s)
Antifungal Agents/pharmacology , Antineoplastic Agents/pharmacology , Aplysia/metabolism , Glycoproteins/pharmacology , Animals , Candida albicans/drug effects , Candida albicans/genetics , Microbial Sensitivity Tests , Saccharomyces cerevisiae/drug effects , Saccharomyces cerevisiae/genetics , Schizosaccharomyces/drug effects , Schizosaccharomyces/genetics
20.
J Biol Chem ; 268(16): 12055-61, 1993 Jun 05.
Article in English | MEDLINE | ID: mdl-8505329

ABSTRACT

An antifungal protein (AFP) was purified from the hemolymph of third instar larvae of Sarcophaga peregrina. This protein repressed the growth of Candida albicans in Sabouraud medium in the presence of nitrofurazone. However, in distilled water or saline, AFP alone killed C. albicans. Significant synergism was detected between AFP and sarcotoxin IA, an antibacterial protein of Sarcophaga. The lethal effect of AFP on C. albicans was greatly enhanced by the presence of a small amount of sarcotoxin IA. AFP was shown to bind to C. albicans and cause leakage of a substance(s) with absorbance at 260 nm from the cells. Analysis of its cDNA showed that AFP is a novel histidine-rich protein consisting of 67 amino acid residues.


Subject(s)
Antifungal Agents/isolation & purification , DNA/genetics , Diptera/metabolism , Insect Proteins , Proteins/genetics , Proteins/isolation & purification , Amino Acid Sequence , Animals , Anti-Infective Agents/pharmacology , Antifungal Agents/pharmacology , Base Sequence , Candida albicans/drug effects , Candida albicans/growth & development , Cloning, Molecular , DNA/isolation & purification , Diptera/genetics , Drug Synergism , Hemolymph/metabolism , Insect Hormones/pharmacology , Larva , Molecular Sequence Data , Molecular Weight , Oligodeoxyribonucleotides , Protein Structure, Secondary , Proteins/pharmacology , RNA, Messenger/analysis , RNA, Messenger/metabolism
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