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Biomedical subjects

Michael Kundi

Publications and source records attributed to Michael Kundi.

At least 55 records · Page 3Linked to original sources

Prevention of heterocyclic amine-induced DNA damage in colon and liver of rats by different lactobacillus strains.

The aim of the present study was to investigate the impact of four different lactobacillus (LB) strains, namely Lactobacillus bulgaricus 291, Streptococcus thermophilus F4, S.thermophilus V3 and Bifidobacterium longum BB536, which are used for the production of yogurt, on the DNA-damaging effects of heterocyclic aromatic amines (HCAs). Male F344 rats were treated orally with HCA mixtures containing 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline, 2-amino-3,4,8-trimethyl-3H-imidazo[4,5-f]quinoxaline, 2-amino-9H-pyrido[2,3-b]indole and 2-amino-3-methyl-3H- imidazo[4,5-f]quinoline, which were representative of the HCA contents found in fried beef ('beef mix') and chicken ('chicken mix'). Suspensions of LB were given by gavage to the animals simultaneously with and at different time periods before administration of the HCAs. Subsequently, the extent of DNA migration was measured in colon and liver cells in single cell gel electrophoresis (SCGE) assays. All four strains caused complete inhibition of DNA damage induced with beef mix after administration of 1 x 1010 LB cells/animal, whereas with chicken mix only marginal (non-significant) effects were seen. The inhibition of beef-induced DNA damage was dose dependent and was still significant when 1 x 107 cells/animal were administered. Kinetics studies showed that the protective effects were still significant when LB was given 12 h before the beef mix. A comparison of the present results with chemical analytical data from in vitro experiments suggests that the strong reduction in DNA migration seen in the animals can be only partly explained by direct binding effects. The results of the present study show that LB are highly protective against the genotoxic effects of HCAs under conditions which are relevant for humans and provide a possible explanation for the reduced colon cancer rates observed in some studies in individuals with either high LB counts in their feces or with a high consumption of LB-containing foods.

Amines↗

Increased risk of mother-to-infant transmission of hepatitis C virus by intrapartum infantile exposure to maternal blood.

Virological and clinical data from 73 hepatitis C virus (HCV)-infected pregnant women who gave birth to 75 children were merged retrospectively, by logistic regression analysis, to investigate risk factors for vertical transmission of HCV. Eighty-two percent of the HCV-infected mothers were HCV-RNA-positive during pregnancy, and 10% were coinfected with human immunodeficiency virus (HIV). Nine children were HCV infected, 1 was HIV infected, but none was HIV-HCV coinfected. Among vaginal deliveries, the mean HCV load of mothers who transmitted HCV to their infants was higher than that of those who did not (8.1 x 10(5) vs. 1.4 x 10(4) copies/mL; P=.056). A reduction in umbilical cord-blood pH (relative risk, 3.9; P=.04) or the occurrence of perineal or vaginal laceration (relative risk, 6.4; P=.028) during vaginal delivery significantly increased the risk of vertical HCV transmission. In conclusion, high maternal viremia, infantile hypoxia, and intrapartum exposure to virus-contaminated maternal blood increased the risk of HCV transmission during vaginal deliveries. Consequently, cesarean section may reduce the risk of vertical HCV transmission in selected cases.

Female↗

Effects of mustard sprouts and allylisothiocyanate on benzo(a)pyrene-induced DNA damage in human-derived cells: a model study with the single cell gel electrophoresis/Hep G2 assay.

The aim of this study was to investigate the chemoprotective effects of mustard sprouts on benzo(a)pyrene [B(a)P]-induced DNA damage in the single cell gel electrophoresis (SCGE)/Hep G2 assay. This model combines the advantages of the SCGE assay with that of human-derived cells that possess inducible phase I and phase II enzymes. Treatment of the cells with small amounts of mustard juice (0.1-1.25 microl/ml) and B(a)P reduced the genotoxic effect of the carcinogen in a dose-dependent manner. Contrary to the results with the juice, unexpected synergistic effects were observed with allyl isothiocyanate (AITC, 0.3 microM), a breakdown product of sinigrin, which is contained in black mustard and many other cruciferous vegetables. Although these concentrations of AITC did not cause DNA damage per se, pronounced dose-dependent DNA damage was seen with higher concentrations of AITC (>or= 25 microM). In parallel with the comet assays, also enzyme measurements were carried out which showed that exposure of the cells to mustard juice (2.0 microl/ml) causes a moderate induction of ethoxyresorufin-O-deethylase, and more pronounced (approximately 2-fold) increase of the activity of glutathione-S-transferase. In conclusion, our findings indicate that i) mustard juice is highly protective against B(a)P-induced DNA damage in human derived cells and ii) that induction of detoxifying enzymes may account for its chemoprotective properties. iii) Furthermore, our findings show that the effects of crude juice can not be explained by its allyl isothiocyanate contents.

Anticarcinogenic Agents↗

Relationship between detection limit and bias of accuracy of quantification of RNA by RT-PCR.

Evidence is presented demonstrating that the distribution of data obtained applying a given RT-PCR method deviates from a normal distribution depending on the limit of detection. The effect of this is a bias towards higher values and concomitantly a systematic error in respect to the accuracy of the evaluation due to this deviation from normality. In addition, evidence is presented that an evaluation assuming a log-normal distribution is more appropriate.

Data Interpretation, Statistical↗

Chemoprevention of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ)-induced colonic and hepatic preneoplastic lesions in the F344 rat by cruciferous vegetables administered simultaneously with the carcinogen.

The aim of this study was to investigate the chemopreventive effects of widely consumed cruciferous vegetables, namely Brussels sprouts and red cabbage towards 2-amino-3-methylimidazo[4,5-f]quinoline (IQ)-induced preneoplastic lesions [liver glutathione-S-transferase placental positive (GST-P(+)) foci and colonic aberrant crypt foci (ACF)]. Male F344 rats were treated with IQ (100 mg/kg bw/g) on 10 alternating days and received drinking water supplemented with Brussels sprouts and red cabbage juices (5% v/v) before and during the carcinogen treatment. From each vegetable two different cultivars were tested. Brussels sprouts reduced the frequency of IQ-induced aberrant foci in both organs (41-52% in the colon and 27-67% in the liver). Also, Brussels sprouts drastically diminished (85-91%) the size of liver GST-P(+) foci, but no such effect was seen in the colon. With red cabbage, the size of liver GST-P(+) foci was markedly reduced (41-83%) whereas the foci frequency was only moderately decreased (19-50%). No protection was seen in the colon after treatment with red cabbage. Cooking (10 min, 100 degrees C) of the vegetables had no influence on their protective effects. The stronger chemoprotective effects of Brussels sprouts may be due to the fact that the overall glucosinolate contents were substantially (2-3-fold) higher than those of the cabbage cultivars, but it was not possible to attribute the reduction of preneoplastic lesions to specific glucosinolates. The activities of hepatic UDP-glucuronosyltransferase form 2 (UDPGT-2) and cytochrome P4501A2 were increased by both vegetables. The induction effect of Brussels sprouts on the activity of UDPGT-2 was more marked than that of the red cabbage cultivars, suggesting that increased glucuronidation of IQ may account for the reduction of the preneoplastic lesions. Our findings support the assumption that Brassica vegetables protect against the carcinogenic effects of heterocyclic amines.

Animals↗

Mobile telephones and cancer: is there really no evidence of an association? (review).

Two Swedish epidemiological studies have shown an association between the use of mobile telephones, mainly of the analogue type, and brain tumours. These findings have been corroborated in a Finnish study. Supportive evidence has also come from studies in USA, but these investigations, as well as a Danish study, are inconclusive due to e.g., few exposed subjects, short latency periods and methodological shortcomings. The Swedish Radiation Protection Authority (SSI) engaged two epidemiologists from a private company to conduct a review of the literature. They claimed that use of mobile telephones is not associated with increased risk for brain tumours. Their conclusion was, however, based on an unbalanced view of current literature in favour of studies showing no association. These circumstances are further explored in this communication.

Brain Neoplasms↗

Duplex sonographic predictors of restenosis, vascular and neurological events after carotid endarterectomy.

BACKGROUND: Although excellent short- and long-term results have been achieved with surgery in extracranial internal carotid artery stenosis, recurrent stenosis continues to play an important role in post-endarterectomy. Therefore, a close follow-up of patients is warranted. The value of postoperative duplex sonographic evaluations in postoperative follow-up is highly disputed. The study evaluates duplex sonographic parameters as predictors of carotid restenosis, general vascular events and ipsilateral neurological symptoms, in order to assess the role of duplex sonography in follow-up after carotid endarterectomy. METHODS: A retrospective cohort study with a follow-up period ranging from 7 months to 7.5 years was performed in 150 patients who underwent carotid endarterectomy. Pre- and postoperative duplex sonographic and clinical data were analyzed by life-table analysis and multivariate Cox regression with respect to carotid restenosis, vascular and ipsilateral neurological events. MAIN FINDINGS: Duplex sonographic predictors of carotid restenosis include the postoperative degree of stenosis (residual stenosis > or = 30% or more: relative risk (RR) = 1.56; 1.05-2.32), pre- to postoperative reduction of stenosis (higher than 50%: RR = 0.61; 0.45-0.83), and residual plaques in the operated carotid artery (RR = 1.96; 1.31-2.93). Some of these morphological parameters such as reduction of stenosis are also predictive of vascular events (RR = 1.25; 1.01-1.56) and ipsilateral neurological events (RR = 1.52; 1.05-2.19). In 12 cases restenosis was discovered by duplex sonography and in 3 cases by evaluation of clinical symptoms. In 5 cases restenosis was treated by repeat surgery. Contralaterally, progressive or newly developed carotid stenoses were observed in 17 cases, and only 5 were discovered on the basis of clinical symptoms. Fourteen contralateral stenoses required surgery. Overall, 12 patients underwent treatment for stroke prevention on the basis of duplex follow-up findings (8% of the study population). CONCLUSIONS: Postoperative duplex sonography allows for the identification of patients at risk for carotid restenosis as well as those at risk for other vascular events. As expected, regular examinations permit early detection of restenosis requiring surgical treatment. However, a large number of contralateral stenoses requiring surgical treatment were detected by routine duplex sonographic examinations. The timing of follow-up intervals may be oriented towards the perioperative outcome of duplex sonography.

Adult↗

Effects of heavy metal contamination of soils on micronucleus induction in Tradescantia and on microbial enzyme activities: a comparative investigation.

The aim of this study was to investigate correlation between genotoxic effects and changes of microbial parameters caused by metal contamination in soils. In total, 20 soils from nine locations were examined; metal contents and physicochemical soil parameters were measured with standard methods. In general, a pronounced induction of the frequency of micronuclei (MN) in the Tradescantia micronucleus (Trad-MN) assay was seen with increasing metal concentration in soils from identical locations. However, no correlations were found between metal contents and genotoxicity of soils from different locations. These discrepancies are probably due to differences of the physicochemical characteristics of the samples. Also, the microbial parameters depended on the metal content in soils from identical sampling locations. Inconsistent responses of the individual enzymes were seen in soils from different locations, indicating that it is not possible to define a specific marker enzyme for metal contamination. The most sensitive microbial parameters were dehydrogenase and arylsulfatase activity, biomass C, and biomass N. Statistical analyses showed an overall correlation between genotoxicity in Tradescantia on the one hand and dehydrogenase activity, biomass C, and the metabolic quotient on the other hand. In conclusion, the results of the present study show that the Trad-MN assay is suitable for the detection of genotoxic effects of metal contamination in soils and furthermore, that the DNA-damaging potential of soils from different origin cannot be predicted on the basis of chemical analyses of their metal concentrations.

Arylsulfatases↗

Genotoxic response of Austrian groundwater samples treated under standardized UV (254 nm)--disinfection conditions in a combination of three different bioassays.

Ground water samples from different geographic areas in Austria, with different amounts of natural and anthropogenic organic compounds were treated with a standardized low pressure UV (254 nm)-irradiation laboratory flow-through system (UV fluence: 800 J/m2). The genotoxic activities of the water samples before and after the UV disinfection were investigated using a combination of three different bioassays which complement each other with regard to their sensitivity detecting different genotoxins. The test battery comprises the Salmonella/microsome assay (Ames test with TA98. TA 100 and TA 102, with and without S9 mix) and two micronucleus tests with the plant Tradescantia (clone #4430) and with primary rat hepatocytes. Overall, the tested Austrian groundwater samples used for human consumption caused only weak genotoxic activities compared to drinking water samples reported from other countries under similar experimental conditions. With the exception of one weak positive result in the Ames test (only in strain TA98 without S9 mix) with an induction factor of 1.9) all samples after UV disinfection were devoid of additional mutagenic and clastogenic activities compared to the samples before UV disinfection.

Animals↗

Horses and Borrelia: immunoblot patterns with five Borrelia burgdorferi sensu lato strains and sera from horses of various stud farms in Austria and from the Spanish Riding School in Vienna.

Grazing animals are continuously exposed to tick bites. Consequently, one may expect that horses will become infected with the various pathogens carried by ticks including Borrelia burgdorferi sensu lato. Whether horses may develop clinical disease due to this pathogen is controversially discussed. We were interested to learn about the infection of horses with Borrelia burgdorferi sensu lato within one season by studying the dynamics of the humoral immune response in paired blood samples. The majority of horses examined were Lipizzaner from the stud farm in Piber/Steiermark, and from the Spanish Riding School in Vienna. Smaller groups of animals of different breeds were from stud farms in Kärnten, Niederösterreich, Salzburg and Steiermark. Clinical status and medical history were obtained and blood was drawn at the beginning of the highest tick activity and nine months later in 1998. Immunoblot technique (Western blot) was used in order to determine the dynamics in the immune response patterns. As antigens served the genospecies Borrelia afzelii, Borrelia burgdorferi sensu stricto, Borrelia garinii, Borrelia lusitaniae, and Borrelia valaisiana. 309 horses (age median 7 years, range 1/12 to 33 years) were seen at the first round. 186 of these animals (60.2%; median age 6 years, range 4/12 to 33 years) were re-examined in the second round. All animals were in normal health condition during both rounds of examination and blood sampling. Analysis of the immunoblot patterns was based on in-house-, Pko-, Pka2-, Pbi-, and European Union Concerted Action on Lyme Borreliosis (EUCALB) 2 & 3-criteria; analyses revealed a variety of positive results with different strains and criteria. Positive immunoblot results with 186 paired samples and B. afzelii as antigen, for example, ranged from 52 to about 91% in the first, and 53 to 93% in the second round. The age dependency analyses showed that the first infection with B. burgdorferi sensu lato occurs in the first year. Re-infection is characterised by appearance of additional bands. Continuously tick-exposed horses show a stable pattern of bands whilst in unexposed horses the number of bands decreases with age. In this study horses became repeatedly infected with B. burgdorferi sensu lato but, apparently, developed only rarely, if at all, clinical diseases. The infectious agent is predominantly B. afzelii. Antibodies to other borrelia genospecies are predominantly due to cross reactivity.

Animals↗

Lead in drinking water of Vienna in comparison to other European countries and accordance with recent guidelines.

Due to the decrease of lead intake via inhalation route, the oral route, particularly from drinking water in cities with lead installations, gains relative importance. In two surveys a total of 288 objects were investigated and 1768 samples were analysed. The first series with 51 objects using a field experimental approach systematically investigated the effects of daytime, floor and flushing. Because only objects built before 1945 and suspected of lead plumbing were chosen, the first series approaches worst case conditions. The second series investigating 237 randomly chosen objects stratified according to time of consumption should allow inferences about the present situation in Viennese households. Each sampling procedure comprised one sample without flushing and three further samples with flushing of 1 l, 3 l and 10 l, respectively. Statistically significant decreases occurred between these flushing conditions. The sampling data of the upper floors showed significantly higher lead contents compared to the lower floors, which indicates that house installations are the main causes of lead contamination in Viennese drinking water. In comparison to other European countries the percentage of samples exceeding the guideline levels (50 micrograms/l as current value and 10 micrograms/l as target value) was lower.

Austria↗

Reliability of nested PCR for detection of Chlamydia pneumoniae DNA in atheromas: results from a multicenter study applying standardized protocols.

The present multicenter study was designed to find explanations for the discrepancies in the reported rates of detection of Chlamydia pneumoniae DNA in endarterectomy specimens. Coded identical sets of (i) a C. pneumoniae DNA dilution series (panel 1; n = 10), (ii) spiked control tissue specimens (panel 2; n = 10 specimens, including 5 negative controls), and (iii) endarterectomy specimens (panel 3; 15 atheromas, 5 negative controls) were analyzed at four laboratories by three standardized DNA extraction methods in each laboratory and a nested touchdown PCR protocol targeting the ompA gene of C. pneumoniae. Panel 1 samples were correctly identified as positive to levels of 0.3 inclusion-forming units (IFU)/PCR mixture (100%) and 0.03 IFU/PCR mixture (50%). All negative controls were correctly reported as negative. Panel 2 samples were identified as C. pneumoniae positive to levels of 0.01 IFU/PCR mixture (100%) and 0.005 IFU/PCR mixture (91%), independent of the DNA extraction method used, and only one false-positive result was reported. For panel 3 samples, 5 of 240 (2%) analyses (in which DNA extractions and PCR were performed at the same laboratory) were positive; the positive specimens were from three endarterectomy specimens and two negative controls. After exchange of DNA extracts between laboratories, 13 of 15 atheroma samples were C. pneumoniae DNA positive in at least 1 of a series of 48 analyses per atheroma sample; however, the overall positivity rate did not exceed 5% (33 of 720 analyses) and therefore was lower than that for the negative controls (8%; 19 of 240 analyses). Not a single positive result could be achieved when all panel 3 extracts (n = 240 analyses) were reamplified by a 16S rRNA PCR followed by hybridization with a C. pneumoniae-specific probe. Statistical analyses demonstrated that positive results did not occur in an independent and random fashion and could most likely be explained by amplicon carryover at the nested PCR level as well as amplicon introduction during DNA extraction, but not by the patterns of distribution of very low target levels or a certain DNA extraction protocol. The results of studies by nested PCR for detection of the prevalence of C. pneumoniae will always be questionable.

Arteriosclerosis↗

Effectiveness of reverse transcription-PCR, virus isolation, and enzyme-linked immunosorbent assay for diagnosis of influenza A virus infection in different age groups.

The degrees of effectiveness of reverse transcription (RT)-PCR, virus isolation, and antigen enzyme-linked immunosorbent assay (ELISA) for the detection of influenza A virus were evaluated with nasopharyngeal swabs from 150 patients (1 week to 86 years old) with influenza A virus infection. RT-PCR had a sensitivity for influenza A virus in stock virus preparations 10(3) times higher than virus isolation and 10(6) to 10(7) times higher than ELISA. The detection rate achieved by RT-PCR in clinical samples was clearly higher (93%) than that by virus isolation (80%) and ELISA (62%). Despite low overall detection rates achieved by antigen ELISA, samples from patients younger than 5 years old yielded higher-than-average rates in this rapid assay (88%). The likelihood of negative results in the ELISA increased significantly with increasing age of the patient (P < 0.01). The degrees of effectiveness of RT-PCR and virus isolation were not influenced by the age of the patient. Neither influenza immunizations nor the interval between onset of symptoms and laboratory investigation (mean, 4.7 days; standard deviation, 3.3 days) affected results obtained by the three test systems. Our results demonstrate that the ELISA is reliable for rapid laboratory diagnosis of influenza in infants and young children, but for older patients application of RT-PCR or virus isolation is necessary to avoid false negative results.

Adolescent↗

Blood pressure responses after carotid surgery: relationship to postoperative baroreceptor sensitivity.

BACKGROUND AND PURPOSE: Among hypertensive patients after carotid surgery, a group of patients with increased baroreflex sensitivity was identified. In the other group of hypertensive patients, blood pressure and reflex sensitivity were unchanged postoperatively. We hypothesized that a partial readjustment of baroreceptor sensitivity would produce more stable blood pressure profiles. METHODS: In order to test this hypothesis, a prospective, long-term follow-up study was designed. Blood pressure was monitored in 18 hypertensive and 6 normotensive patients during 6 months using a self-measurement technique. In addition, continuous 24-hour blood pressure monitoring was performed 6 months after surgery. The mean values and the ranges (amplitudes) of systolic and diastolic blood pressure were calculated as indicators for the stability of the circulatory system. RESULTS: Hypertensive patients with unchanged postoperative baroreceptor sensitivity showed significantly more pronounced instabilities of their blood pressure profiles (amplitudes of systolic and diastolic blood pressure p < 0.05 to p < 0.001). A relationship between baroreceptor function and antihypertensive therapy could also be demonstrated, with adequate therapy being much more difficult in patients with reduced or unchanged baroreceptor sensitivity. CONCLUSIONS: In contrast to vascular surgery on the aorta or in the region of the lower limbs, carotid surgery is frequently associated with blood pressure changes, demonstrating the essential role of the baroreceptors in the carotid sinus for the regulation of postoperative blood pressure. Since it seems to be the variability of blood pressure, and not the blood pressure level alone, that is critical, close blood pressure monitoring--allowing for an assessment of blood pressure variability--appears to be of particular importance in such patients.

Aged↗

Development and application of test methods for the detection of dietary constituents which protect against heterocyclic aromatic amines.

This article describes the development and use of assay models in vitro (genotoxicity assay with genetically engineered cells and human hepatoma (HepG2) cells) and in vivo (genotoxicity and short-term carcinogenicity assays with rodents) for the identification of dietary constituents which protect against the genotoxic and carcinogenic effects of heterocyclic aromatic amines (HAs). The use of genetically engineered cells expressing enzymes responsible for the bioactivation of HAs enables the detection of dietary factors that inhibit the metabolic activation of HAs. Human derived hepatoma (HepG2) cells are sensitive towards HAs and express several enzymes [glutathione S-transferase (GST), N-acetyltransferase (NAT), sulfotransferase (SULT), UDP-glucuronosyltransferase (UDPGT), and cytochrome P450 isozymes] involved in the biotransformation of HAs. Hence these cells may reflect protective effects, which are due to inhibition of activating enzymes and/or induction of detoxifying enzymes. The SCGE assay with rodent cells has the advantage that HA-induced DNA damage can be monitored in a variety of organs which are targets for tumor induction by HAs. ACF and GST-P(+) foci constitute preneoplastic lesions that may develop into tumors. Therefore, agents that prevent the formation of these lesions may be anticarcinogens. The foci yield and the sensitivity of the system could be substantially increased by using a modified diet. The predictive value of the different in vitro and in vivo assays described here for the identification of HA-protective dietary substances relevant for humans is probably better than that of conventional in vitro test methods with enzyme homogenates. Nevertheless, the new test methods are not without shortcomings and these issues are critically discussed in the present article.

Anticarcinogenic Agents↗