Biomedical subjects

I Huk

Publications and source records attributed to I Huk.

At least 19 recordsLinked to original sources

PubMed2006

No evidence for a direct role of Helicobacter pylori and Mycoplasma pneumoniae in carotid artery atherosclerosis.

BACKGROUND: That infections with certain pathogens, by initiating an inflammatory response, may contribute to the development of atherosclerosis is suggested by clinical and experimental evidence. AIM: To analyse atherosclerotic plaques of the carotid artery, samples of apparently healthy greater saphenous veins and circulating leucocytes from the same individual patients for the presence of Helicobacter pylori and Mycoplasma pneumoniae. METHODS: Samples from 36 patients undergoing carotid endarterectomy for symptomatic carotid artery stenosis were analysed by polymerase chain reaction for the presence of DNA specific for H. pylori and M. pneumoniae. IgG antibody titres against H. pylori and M pneumoniae and plasma levels of soluble E-selectin, soluble intercellular adhesion molecule-1 and soluble vascular cell adhesion molecule-1 were determined. RESULTS: M. pneumoniae-specific DNA was detected in the atherosclerotic plaques of 13 of 36 (36.1%) patients, in the saphenous veins of 9 of 36 (25%) patients and in the leucocytes of 27 of 36 (75%) patients. No salient association was observed between the presence of M. pneumoniae-specific DNA in leucocytes and atherosclerotic plaques or veins. A marked correlation between the presence of M. pneumoniae in the respective specimens and the studied inflammatory markers or the presence of anti-M. pneumoniae antibodies was not observed. H. pylori-specific DNA could not be detected in the specimens tested. CONCLUSIONS: The absence of H. pylori and the random distribution of M. pneumoniae in tissue samples obtained from patients with symptomatic carotid artery stenosis do not support a role for these pathogens in the development of atherosclerosis due to a direct interaction of the bacteria with the vasculature.

Aged↗

PubMed2003

The impact of endovascular stent grafting on reducing mortality rates after surgical treatment of abdominal aortic aneurysms.

OBJECTIVES: to investigate whether appropriate selection in patients with infrarenal abdominal aortic aneurysms (AAA) for transfemoral endovascular aneurysm management (TEAM) or open graft replacement (OGR) may decrease in-hospital mortality rates (MR). DESIGN: analysis of a clinical series over three periods in an university vascular center. Conclusions of the second period were drawn and prospectively applied in a third period and compared. METHODS: during the period 1989-1994 only OGR was available (n=170). In the interval 1995-2000 either OGR or TEAM were carried out (n=454). During the period 01/2001-07/2002 the conclusions concerning selection of treatment modality were drawn and prospectively applied in 132 consecutive patients. MR were recorded and possible significant differences were checked. RESULTS: during the first period MR was 6.5%. Overall MR decreased to 3.7% in the second interval. Overall MR of the last period was improved to 1.5% (p<0.05). No patient died after OGR (0% vs 6.5%, p<0.04). As all patients with significant individual risk profiles were treated by TEAM, MR slightly increased (2.9%), but the difference remained insignificant (2.4% in period 2). CONCLUSIONS: risk adjusted selection of treatment modality influences the results after OGR significantly, thereby reducing overall MR of elective AAA treatment.

Aged↗

PubMed2003

Delivery of high dose VEGF plasmid using fibrin carrier does not influence its angiogenic potency.

Delivery of DNA mixed with a degradable matrix carrier was supposed to improve transgene expression. Using a rabbit hind-limb ischemia model, we tested the angiogenic potency of plasmid encoding human vascular endothelial growth factor (pSG5-VEGF165) entrapped in fibrin sealant. Animals were injected intramuscularly with 500 microg of pSG5-VEGF165 or control plasmid, dissolved in saline (PBS) or fibrin glue. After 14 days, presence of delivered constructs and expression of transgene was confirmed in injected muscles of all animals. There were no significant differences in the levels of human VEGF mRNA and protein between VEGF-PBS and VEGF-fibrin groups (Mann-Whitney test). Accordingly, pSG5-VEGF165 regardless of the way of delivery, induced similar increases in capillary density within treated muscles (ANOVA). Control plasmid did not show any effects. In conclusion, injection of pSG5-VEGF165 into ischemic adductor muscle leads to synthesis of human VEGF and increases the number of capillaries. Fibrin carrier does not influence its angiogenic potential.

Animals↗

PubMed2001

Genetic augmentation of nitric oxide synthase increases the vascular generation of VEGF.

OBJECTIVE: Vascular endothelial growth factor (VEGF) induces the release of nitric oxide (NO) from endothelial cells. There is also limited data suggesting that NO may enhance VEGF generation. METHODS: To further investigate this interaction, we examined the effect of exogenous and endogenous NO on the synthesis of VEGF by rat and human vascular smooth muscle cells (VSMC) by exposing cells to exogenous NO donors, or to genetic augmentation of eNOS or iNOS. RESULTS: NO-donors potentiated by 2-fold the generation of VEGF protein by rat or human VSMC. Similarly, rat or human VSMC transiently transfected with plasmid DNA encoding eNOS or iNOS, synthesized up to 3-fold more VEGF than those transfected with control plasmid DNA, an effect which was reversed after treatment with the NOS antagonist L-NAME. Rat VSMC stably transfected with pKeNOS plasmid, constitutively produced NO and released high concentrations of VEGF. In these cells, L-NAME significantly reduced NO synthesis and decreased VEGF generation. The VEGF protein produced by NOS-transfected VSMC was biologically active, as conditioned media harvested from these cells increased endothelial cell proliferation. CONCLUSION: These studies reveal that NO derived from NO-donors or generated by NOS within the cells, upregulates the synthesis of VEGF in vascular smooth muscle cells. Administration of NO donors, or augmentation of endogenous NO synthesis, may be an alternative approach in therapeutic angiogenesis.

Analysis of Variance↗

PubMed2001

Prostaglandin-J2 induces synthesis of interleukin-8 by endothelial cells in a PPAR-gamma-independent manner.

PPARgamma is a transcription factor of nuclear receptor superfamily, involved in the regulation of inflammation. We investigated the influence of PPARgamma-ligands, 15-deoxy-delta12,14 prostaglandin-J2 (15d-PGJ2), and ciglitazone, on the generation of interleukin-8 (IL-8) by the human microvascular endothelial cell line (HMEC- 1). Expression of PPARgamma in HMEC-1 was confirmed by RT-PCR. Both PPARgamma-ligands tested induced the activation of PPAR, but the potency of ciglitazone was higher, as evidenced by luciferase assay. Resting HMEC-1 released about 150 pg/ml of IL-8 protein. Treatment with LPS increased the IL-8 secretion up to 1 ng/ml. 15d-PGJ2 potently and dose-dependently increased both the steady-state and LPS-induced generation of IL-8 mRNA and IL-8 protein. In contrast, neither basal nor LPS-elicited expression of IL-8 was influenced by ciglitazone. We conclude, that 15d-PGJ2 is a potent inducer of IL-8 production and can be a mediator of inflammatory response, but this effect is independent of PPARgamma activation.

Cell Line↗

PubMed2001

Collagen versus gelatin-coated Dacron versus stretch polytetrafluoroethylene in abdominal aortic bifurcation graft surgery: results of a seven-year prospective, randomized multicenter trial.

BACKGROUND: A prospective randomized multicenter trial was performed to compare knitted gelatin-coated Dacron bifurcation grafts, knitted collagen-coated Dacron grafts, and stretch polytetrafluoroethylene (PTFE) grafts. METHODS: Between 1991 and 1998, 315 elective patients were randomized by age, gender, diabetes, runoff, indication (aneurysm, aortoiliac occlusive disease), and nicotine consumption at 3 centers of vascular surgery in Austria. The patients received gelatin-coated Dacron (GEL-D) grafts (n = 109), collagen-coated Dacron (COL-D) grafts (n = 100), or stretch PTFE grafts (n = 106). RESULTS: No intraoperative deaths occurred. The 30-day mortality was 3%. No difference was found between the 3 graft materials in long-term patency. The primary 5-year patency rates were 92% for GEL-D, 89% for COL-D, and 91% for stretch PTFE (P =.6001). The secondary 5-year patency rates also differed: 97% for GEL-D, 100% for COL-D, and 97% for stretch PTFE (P =.2062). Early occlusions were observed overall in 3% and late occlusions in 5% of patients. When both Dacron grafts were compared collectively with stretch PTFE, a difference was found in infection rate: Dacron 3% (6/209) versus PTFE 0% (0/106); P <.03. CONCLUSIONS: The bifurcation grafts of all 3 materials were comparable in primary and secondary patency rates, incidence of false aneurysms, and rate of perioperative complications. Graft infections were confined to the 2 Dacron grafts and did not occur in stretch PTFE grafts.

Aorta, Abdominal↗

PubMed2001

[Endovascular (transfemoral endoluminal aneurysm management; TEAM) versus conventional open therapy in abdominal aortic aneurysms (AAA): analysis of a clinical series].

All patients (n = 826) treated electively at the Department of Vascular Surgery University of Vienna, Austria, for their AAA during the years 1965-2000 were analysed with particular emphasis on endoluminal repair. Data collection was carried out in retrospect. The operative mortality or within 30 days was considered the primary endpoint of the study. Since 1995 the TEAM approach was available. From that point in time 45.5% of the AAA were treated electively in the endoluminal way. An exploratory analysis of the clinical series revealed a statistically significant difference in the incidence of various risk factors between groups in favor of open repair. Consequently a conditional regression analysis demonstrated the operative method, median patient's age (above versus below 72 years of age), reduced renal and/or pulmonary function to be of significant influence.

Aged↗

PubMed2001

[Preoperative risk factors as deciding criteria in surgical treatment strategy of infrarenal aortic aneurysm].

Significant risk factors of operative therapy in patients with infrarenal aortic aneurysms (AAA) were determined. Best treatment strategy (open surgical repair, transluminal endovascular aneurysm management (TEAM) or conservative treatment) was selected on the base of evaluated risk factors, tendency of rupture and life expectancy. Of the typical risk factors impaired renal and/or lung function showed a significant influence on hospital mortality. In patients without these significant risk factors open surgical repair leads to good clinical results. Acceptable postoperative mortality rates after elective exclusion of an AAA with average size in patients presenting significant comorbidities can only be achieved using TEAM. If TEAM can not be performed, open surgery is only justified in the case of very large AAA diameter.

Aged↗

PubMed2001

[Clinical research in a university hospital--how we do it in Austria].

Evaluation of quality of work in surgical society is based in clinical and scientific output. Scientific quality of the publications is calculated on the basis of impact factors of journal ranking. Clinical evaluation is based on catalogues of operations performed and voluntary examination in a special surgical field. Total scientific output increased in Austria during the last decade achieving higher level as compared to Germany but lower than in Switzerland. Scientific and clinical standards in a teaching institutions should be kept high allowing candidates to succeed in competition for top positions.

Austria↗

PubMed2000

Vascular surgery between the millenniums.

Modern diagnostic modalities as well as ongoing improvement of vascular prosthetic material and surgical techniques have stimulated progress in vascular surgery. New discoveries concerning the mechanism of endothelial function, atherosclerosis, developments in gene therapy and endovascular techniques will expand the future therapeutic spectrum of vascular surgery. Endoluminal implantation of stent grafts for the treatment of aortic aneurysm may be a reasonable alternative to conventional surgery, especially in high-risk patients. Long-term results of this procedure, however, are not yet available. Stenting of internal carotid artery stenosis may be considered as an experimental method of treatment. Its feasibility, efficacy, safety and long-term results must be analyzed before the application of the method may be restricted or recommended. Endoluminal irradiation (brachytherapy) reduces intimal hyperplasia/restenosis and can improve the long-term results of percutaneous transluminal angioplasty. Anti-atherosclerotic and anti-aggregatory therapy (with statins, estrogens, antibiotics, nitric oxide precursor/donors, glycoprotein IIb/IIIa receptor inhibitors) will play an important role in the prevention of ischemic diseases and improve the results of surgical/interventional treatment by reducing intimal hyperplasia and restenosis. Gene therapy opens new vistas in vascular medicine. Angiogenetic factors can be used for the treatment of patients with distal occlusion of the peripheral arteries. Gene transfer may be useful in the conservative treatment of progressive aortic aneurysms. A more unified vision toward vascular medicine might be the key for research and development in the future.

Aortic Aneurysm↗

PubMed2000

Prostaglandin E1 reduces ischemia/reperfusion injury by normalizing nitric oxide and superoxide release.

To test the effects of prostaglandin E1 on 2.5 h of ischemia followed by 2 h of reperfusion, continuous nitric oxide measurements (electrochemical) were correlated with intermittent assays of superoxide and peroxynitrite levels (chemiluminescence) and ischemia/reperfusion injury in rabbit adductor magnus muscle. Administering prostaglandin E1 (1 microg/kg) before or during ischemia/reperfusion caused normalization of the release of nitric oxide, superoxide, and peroxynitrite to slightly above preischemic levels. This pattern was dramatically different from that observed during ischemia/reperfusion alone, where nitric oxide concentration increased three times above its basal level. Normalization of constitutive nitric oxide synthase activity in the presence of prostaglandin E1 was associated with a significant reduction of superoxide and peroxynitrite production and subsequent reduction of ischemia/reperfusion injury. At 2 h of reperfusion, vasoconstriction associated with ischemia/reperfusion injury was eliminated, and edema was significantly mollified but still apparent. Prostaglandin E1 treatment does not directly inhibit constitutive nitric oxide synthase, like the inhibitor N(omega)-monomethyl-L-arginine. Some phenomenon associated with ischemia turns on endothelial constitutive nitric oxide synthase to start transforming L-arginine and oxygen into nitric oxide, but prostaglandin E1 seems to inhibit this phenomenon. Thus, essential local L-arginine pools are not depleted, and normal basal levels of essential nitric oxide are maintained, whereas cytotoxic superoxide and peroxynitrite production by L-arginine-deficient constitutive nitric oxide synthase is prevented.

Acetylcholine↗

PubMed2000

[Abdominal vascular surgery emergencies: abdominal aortic aneurysm, acute mesenteric ischemia--indications, technique, results].

Ruptured infrarenal aortic aneurysms and mesenteric ischemia are abdominal emergency situations, which should be treated by vascular surgeons. Modern means of patient transport and specialized emergency centers make it possible to bring patients suspect of having a ruptured aneurysm or a mesenteric ischemia to experienced clinics. Indication for surgery in case of symptomatic or ruptured aortic aneurysms is doubtless absolute. If there is suspicion for a ruptured aneurysm, emergency operation is indicated. In patients having undergone emergency surgery for a ruptured aneurysm of the infrarenal aorta, hospital mortality was 41%. The initial indication for surgery for patients with mesenteric ischemia usually is the "acute abdomen". Mostly only the patient's history reveals the suspicion for this disease. There are no valid radiologic examinations for proving or ruling out mesenteric ischemia. Most of our patients had arterial embolism (64%) as a source of mesenteric ischemia, followed by arterial thrombosis (28%), venous thrombosis (3%) and non-occlusive ischemia (5%). Monitoring of levels of serum lactate can be an additional tool for decision making, if a second look operation is discussed. The key for surgical success with these critically ill patients is shortening of the interval between the first symptoms of the patient and the start of surgical therapy.

Aged↗

PubMed1999

Detection of Chlamydia pneumoniae DNA in atheromatous tissues by polymerase chain reaction.

Chlamydia pneumoniae is an important human respiratory pathogen. Recently, seroepidemiological data and the demonstration of chlamydial DNA or antigen within parts of atherosclerotic lesions have suggested a causal association between chlamydial infections and atherosclerosis. As the results obtained by different groups show considerable variations, we provide further data based on a highly specific and sensitive nested PCR method. Positivity was confirmed by nonradioactive hybridization with a specific probe, and sensitivity was determined by titration experiments. C. pneumoniae DNA was detected in 8/29 (28%) of carotid artery samples and 3/14 (21%) of aortic aneurysms.

Aged↗

PubMed1999

Multivitamin administration before ischemia reduces ischemia-reperfusion injury in rabbit skeletal muscle.

This study investigated the effect of a multivitamin preparation administered before ischemia or before reperfusion, on ischemia-reperfusion (I/R) injury of skeletal muscle. An in vivo hindlimb skeletal muscle I/R model (2.5 h/2 h) was carried out on adult New Zealand white rabbits. Animals used as I/R models were treated with a multivitamin preparation (0.4 ml/kg bw i.v. bolus), containing alpha-tocopherol, ascorbic acid, retinol, vitamin B complex, 30 min before starting ischemia (group MV(isc)) or 5 min before reperfusion (group MV(rep)) and compared to animals with I/R without treatment (group IR) and sham operated animals (group SHAM). Interstitial edema (muscle interfiber area, %MIFA) and changes in microvessel size (microvessel cross sectional area, MVCSA, microm(2)) were measured. Plasma malondialdehyde concentrations (MDA-TBA, nmol/ml) served as a measure of lipid peroxidation. After 2h of reperfusion, ischemia-reperfusion developed a significant microvascular constriction and an interstitial edema (IR, vs SHAM;P<< 0.01), but administration of antioxidative vitamins before the onset of ischemia reduced microvascular constriction and edema formation (P<< 0.05 vs IR group). In a similar manner, administration of vitamins before ischemia lowered plasma MDA-TBA levels as compared to the untreated group during reperfusion (p<< 0. 05). In animals treated with vitamins before reperfusion, the biochemical and morphological results showed no differences as compared to the untreated group. Antioxidative treatment with a multivitamin preparation exerted a beneficial effect on I/R injury of skeletal muscle when the aforementioned vitamins were administered before ischemia but not before the onset of reperfusion.

Animals↗

PubMed1999

Nitric oxide mediates the mitogenic effects of insulin and vascular endothelial growth factor but not of leptin in endothelial cells.

The regulation of vascular wall homeostasis by nitric oxide (NO) generated by endothelium is being intensively studied. In the present paper, the involvement of NO in the vascular endothelial growth factor (VEGF), insulin or leptin-stimulated proliferation of human endothelial cells (HUVEC) was measured by [3H]thymidine or bromodeoxyuridine incorporation. VEGF and insulin, but not leptin, increased NO generation in HUVEC, as detected with ISO-NO electrode. Proliferation of HUVEC induced by leptin was not changed or was higher in the presence of N(omega)-nitro-L-arginine methyl ester (L-NAME) a nitric oxide synthase (NOS) inhibitor. In contrast, L-NAME blunted the proproliferative effect of VEGF and insulin. Furthermore, we demonstrated that, in human arterial smooth muscle cells (hASMC) transfected with endothelial NOS (eNOS) gene, the generation of biologically active VEGF protein was NO-dependent. Inhibition of NO generation by L-NAME decreased the synthesis of VEGF protein and attenuated HUVEC proliferation induced by conditioned media from transfected hASMC. Endothelium-derived NO seems to participate in VEGF and insulin, but not leptin, mitogenic activity. Additionally, the small amounts of NO released from endothelial cells, as mimicked by eNOS transfection into hASMC, may activate generation of VEGF in sub-endothelial smooth muscle cells, leading to increased synthesis of VEGF protein necessary for turnover and restitution of endothelial cells.

Cell Division↗

PubMed1998

L-arginine treatment in ischemia/reperfusion injury.

We tested whether treatment with exogenous L-arginine, the precursor of nitric oxide (NO), could protect the skeletal muscle from ischemia/reperfusion (I/R) injury. A rabbit hindlimb I/R model (2.5 h ischemia/2 h reperfusion) was used. Morphological changes were elucidated by morphometry. Plasma concentrations of malondialdehyde (pMDA), as well as L-arginine and L-citrulline content in the plasma and skeletal muscle were measured. I/R injury in the skeletal muscle was manifested by development of prominent interstitial edema (fraction of interfiber area was 26.23% vs 15.09% in sham operated control, p < .005) and severe microvascular constriction (capillary area was 11.41 microns2 vs 16.92 in control, p <.005). These changes were accompanied by increased pMDA levels, indicating a process of lipid peroxidation in the cell membranes. L-arginine treatment (4 mg/kg/min intravenously, for 1 h, infusion initiated 30 min before reperfusion) caused an intracellular accumulation of this amino acid in the SM. Intracellular concentrations of L-citrulline increased (201.0 mumol/dm3 after reperfusion vs 176.0 before ischemia onset, p < .005), suggesting stimulated endogenous NO synthesis. L-arginine treatment protected capillary constriction (capillary area was 17.64 microns2 vs 11.41 in the untreated animals, p < .0005) and reduced interstitial edema after reperfusion (fraction of interfiber area was 17.80% vs 26.23 in untreated animals, p < 0.005). The protective effect of L-arginine treatment on I/R injury of SM may be related to its ability to prevent microvascular constriction and reduce permeability disorders by the stimulation of endogenous NO production.

Animals↗

PubMed1998

Effect of alpha-tocopherol pretreatment on high energy metabolites in rabbit skeletal muscle after ischemia-reperfusion.

The ability of skeletal muscle to recover high energy phosphate compounds in response to pretreatment with vitamin E was investigated in a rabbit hindlimb ischemia/reperfusion model (2. 5 h/2 h). High energy metabolites were measured in the adductor magnus muscle of untreated animals and compared to the treatment group (all rac-alpha-tocopheryl acetate, 3 mg/kg body weight, supplemented i.v. before the onset of ischemia). Phosphocreatine (PCr) levels decreased after ischemia more than 65% in untreated and treatment groups, but tended to recover in treatment group after reperfusion. Adenosine triphosphate (ATP) values decreased by 50% of basal level after reperfusion in the untreated group, whereas alpha-tocopherol pretreatment prevented ATP depletion.

Adenosine Triphosphate↗

PubMed1998

Bioflavonoid quercetin scavenges superoxide and increases nitric oxide concentration in ischaemia-reperfusion injury: an experimental study.

BACKGROUND: L-Arginine-depleted environments accompanying ischaemia-reperfusion enhance superoxide production, leading to the formation of reactive oxygen species and a concomitant reduction in basal nitric oxide levels. The bioflavonoid quercetin may prevent these undesirable effects by scavenging superoxide. METHODS: Untreated rabbits were compared with those infused with quercetin (5 mg/kg for 2 min) during hindlimb ischaemia (2.5 h) and reperfusion (2 h). In both groups, nitric oxide concentration was measured (porphyrinic microsensor) in the femoral artery wall. Microvasculature changes (morphometry) and superoxide concentration (chemiluminescence) were measured intermittently in biopsies. RESULTS: Approximately 6 min into the period of ischaemia a rapid increase in nitric oxide level from a mean(s.e.m.) basal level of 50(20) to 450(30) nmol/l was observed. In untreated animals, nitric oxide concentration dropped to an undetectable level (less than 1 nmol/l) during reperfusion. In quercetin-treated animals, the decrease in nitric oxide concentration was slower, such that substantial amounts (60(20) nmol/l) accumulated during reperfusion. In biopsies after ischaemia-reperfusion maximal calcium ionophore A23187-stimulated nitric oxide concentration increased (25-30 per cent) in the presence of quercetin, while the superoxide concentration decreased. CONCLUSION: Quercetin treatment mollified ischaemia-reperfusion injury to skeletal muscle by scavenging destructive superoxide and enhancing the cytoprotective nitric oxide concentration.

Animals↗