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A Hartmann

Publications and source records attributed to A Hartmann.

At least 73 records · Page 4Linked to original sources
PubMed2001

Caspase-3 activation in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice.

In 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) models of Parkinson's disease (PD), dopaminergic (DA) neurons have been shown to die by apoptosis. Moreover, recent postmortem and in vitro results have indicated that apoptotic cell death induced by 1-methyl-4-phenylpyridinium (MPP(+)) may be mediated by caspase-3. To establish whether caspase-3 activation may indeed play a role in an in vivo model of PD, we studied caspase-3 activation in C57Bl/6 mice subchronically intoxicated with MPTP. We show that caspase-3 activation peaks early, at days 1 and 2 after the end of MPTP intoxication. In contrast, pycnotic neurons persist until day 7 postintoxication, indicating that caspase-3 activation is an early and transient phenomenon in apoptotic death of DA neurons. We further demonstrate that loss of tyrosine hydroxylase (TH) immunoreactivity in this model is indeed due to cell loss rather than to loss of TH protein expression. We conclude that mice subchronically intoxicated with MPTP represent a valid PD model to study and manipulate caspase activation in vivo.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed2001

Naftidrofuryl in the treatment of vascular dementia.

The design of this study was based on the European guidelines for the treatment of Alzheimer's disease. After a placebo run-in period of 4 weeks, patients with a diagnosis of vascular dementia (VaD) were randomised to receive either 400 mg naftidrofuryl/day, 600 mg naftidrofuryl/day or placebo for 6 months. The patients were assessed using the ADAS-cog, the SCAG, the NOSGER and the CGI item 2 scale. The primary analysis was undertaken on the ITT population. At the end of the study, significantly more patients in the treatment groups showed no deterioration on both ADAS-cog and SCAG scales compared with placebo (400 mg p = 0.005, 600mg p = 0.015). There were also significant differences between the active and placebo groups for the individual scales. This study has demonstrated that treatment with naftidrofuryl can slow the rate of deterioration of patients with vascular dementia.

Aged↗
PubMed2001

A new type of exocrine gland and its function in mass recruitment in the ant Cylindromyrmex whymperi (Formicidae, Cerapachyinae).

Workers of the ant Cylindromyrmex whymperi display mass trail recruitment. Bioassays show that the trail pheromone originates from a unique gland between abdominal sternites 6 and 7. The gland has a hitherto unknown structural organization. Upon leaving the secretory cell, the duct cell widens to form a sclerotized pear-shaped reservoir chamber, lined with multiple duct cells. Each duct thus forms a miniature reservoir for the secretions of each single secretory cells, a novel structural arrangement in exocrine glands of social Hymenoptera.

Abdomen↗
PubMed2001

[Is brain blood supply affected by changes in cardiac volume? Measurements of brain blood supply in healthy subjects during volume overload and in patients with artificial pacemaker by changing the pacing rate].

A constant cerebral blood flow (CBF) in the presence of systemic blood pressure changes and cardiac output (CO) alterations during physiological conditions are postulated by the mechanism of cerebral autoregulation. The aim of the present study is the analysis of CBF in pacemaker (PM) patients with unspecific neurological symptoms. CBF was measured in 9 controls and 23 pacemaker patients with 133xenon, CO using Doppler echocardiography or impedance cardiography. Mean and individual CBF in controls remained unchanged when a CO increase of 28% induced by volume overload was observed. In PM patients a mean CO increase of 38% induced by an increase of basic pacing rate caused different effects of CBF. CBF increased or decreased by about 10% or remained constant. In summary, the data suggest an impairment of cerebrovascular function in those patients with concomittant CBF changes due to CO alterations (15/23 approximately equal to 65%). Thus, the analysis of brain perfusion in PM patients with unspecific neurological symptoms is possibly a new diagnostic feature in the future. It can be discussed whether or not indication and optimizing of pacemaker therapy has to be additionally analyzed by determination of endorgan perfusion.

Adult↗
PubMed2001

Changes of cerebral blood flow following dexamethasone treatment in brain tumour patients. A Xe/CT study.

BACKGROUND: It is not exactly known how dexamethasone improves the function of brain that is affected by tumour. Whether and in what sense dexamethasone influences cerebral blood flow has rarely been addressed and previous investigations have yielded inconsistent results. METHOD: Stable xenon-enhanced computed tomography (Xe/CT) was used to assess the regional cerebral blood flow (rCBF) in 67 patients with supratentorial primary and secondary brain tumours. rCBF studies were done at least once prior to resection or stereotactic biopsy of the tumours. In nine patients repeated studies before surgery and in 15 patients additional studies after resective surgery were obtained. Dexamethasone was administered according to the clinical needs before surgery and systematically after surgery. Of the preoperative studies 30 were obtained before and 47 during dexamethasone treatment. The rCBF data were analysed upon correlations with daily dose, cumulative dose, and duration of dexamethasone treatment. Moreover, individual courses before and after surgery were examined. FINDINGS: Mainly inverse correlations were found between the treatment parameters, particularly the daily dose of dexamethasone, and rCBF. Only in the subgroup of glioblastoma patients, a positive correlation was found of both duration and cumulative dose of dexamethasone with rCBF in oedema. Serial observations of individual patients confirmed the above findings, yet with possible exceptions. After tumour resection a clear improvement of rCBF was regularly observed. INTERPRETATION: The beneficial effect of dexamethasone is not attributed to an increase of cerebral blood flow, because rather decreases of rCBF are mostly observed.

Adult↗
PubMed2001

Use of the alkaline comet assay for industrial genotoxicity screening: comparative investigation with the micronucleus test.

We evaluated the suitability of the alkaline comet assay as a screening test in industrial routine testing of new chemicals. Thirty-six pharmaceutical compounds with unknown genotoxic potential were tested comparatively in the comet assay and micronucleus test (MNT) using V79 Chinese hamster cells. The comparison of results is generally based on at least two independent experiments, each with two replicate cultures at a minimum of three concentrations. We found a high degree of concordance between results of the comet assay and MNT. All compounds with negative MNT results were also negative in the comet assay. All positive compounds in the comet assay were also positive in the MNT. However, 16 of 38 positive MNT results were negative in the comet assay. Some of the contrary findings may be due to aneugenic effects, which are detected in the MNT but not in the comet assay. However, the majority of the contrary results may be a consequence of cytotoxicity, which can induce elevated micronucleus frequencies but may not lead to positive effects in the comet assay. Additional data of 39 compounds tested in the Ames test and the comet assay were compared. Four of these compounds that were Ames positive were also positive in the comet assay. However, the comet assay also detected 16 compounds that were negative in the Ames test. We believe that the comet assay in vitro is a useful, fast screening system in mammalian cells that can be used in a test battery during drug development.

Animals↗
PubMed2001

Efficacy of nifedipine or lisinopril in the treatment of hypertension after renal transplantation: a double-blind randomised comparative trial.

Calcium channel blockers and angiotensin converting enzyme-inhibitors are commonly used in the treatment of hypertensive renal transplant recipients. The purpose of this study was to investigate if the response rate to treatment differs with these drugs in this setting. A single centre, prospective, randomised, double-blinded, comparative study to address the efficacy of controlled release nifedipine or lisinopril in the treatment of hypertension (diastolic blood pressure > or =95 mmHg) in cyclosporin (CsA)-treated renal transplant recipients was performed. Recipients were randomised to receive either lisinopril (10 mg once daily) or controlled release nifedipine (30 mg once daily). The dose was doubled on indication. The number of responders (diastolic blood pressure <90 mmHg on monotherapy) were addressed during the early post-transplant phase (first 3 months) and during a late post-transplant phase (from 3 to 12 months after renal transplantation) in the same patient population. One hundred and fifty-four patients (nifedipine=78, lisinopril=76) with untreated hypertension (diastolic blood pressure> or =95 mmHg) were randomised within 3 wk after renal transplantation. One hundred and twenty-three patients (nifedipine=69, lisinopril=54) completed the study. Fourteen (20%) nifedipine-treated recipients responded during the early, and 26 (38%) during the late post-operative phase (months 4-12 after renal transplantation). Eleven (20%) lisinopril-treated recipients responded during the early, and 18 (33%) during the late post-transplant phase. Non-responders were, on average, 8.5+/-1.5 kg heavier both in the early phase and after 1 yr of treatment (p<0.01), and 6.1+/-0.9 yr older than responders (p<0.05). In conclusion, these results indicate that both controlled release nifedipine and lisinopril are equally efficient in the treatment of post-transplant hypertension. As monotherapy, both drugs show a "response rate" of 20-38%, depending on time interval after transplantation.

Adult↗
PubMed2001

Bilateral pharmacokinetic interaction between cyclosporine A and atorvastatin in renal transplant recipients.

Atorvastatin is increasingly used as a cholesterol-lowering agent in solid organ transplant recipients receiving cyclosporine A (CsA). However, the potential bilateral pharmacokinetic interaction between atorvastatin and CsA in renal transplant recipients has not previously been examined. Baseline 12-h CsA pharmacokinetic investigation was performed in 21 renal transplant recipients and repeated after 4 weeks of atorvastatin treatment (10 mg/ d). At week 4, 24-h pharmacokinetics of atorvastatin was also performed. All patients received basiliximab induction followed by CsA and prednisolone immunosuppression. Compared with historic controls, CsA-treated patients showed, on average, sixfold higher plasma HMG-CoA reductase inhibitory activity after 4 weeks of atorvastatin treatment (p < 0.05). Atorvastatin had a moderate effect on the pharmacokinetics of CsA and reduced the AUC0-12 (area under curve, 0-12h) by 9.5 +/- 18% (p = 0.013) and Cmax (maximal concentration) by 13.5 +/- 24% (p =0.009), while C12 (trough level) was unchanged (p =0.42). Total and LDL cholesterol decreased by 26.8 +/- 8.4% (p < 0.0001) and 41.5 +/- 11.0% (p < 0.0001), respectively. Bilateral pharmacokinetic interaction between atorvastatin and CsA resulted in sixfold higher plasma HMG-CoA reductase inhibitory activity, but only a moderate decrease in systemic exposure of CsA.

Adult↗
PubMed2001

Is Bax a mitochondrial mediator in apoptotic death of dopaminergic neurons in Parkinson's disease?

Bax is a proapoptotic member of the Bcl-2 family of proteins. It is believed to exert its action primarily by facilitating the release of cytochrome c from the mitochondrial intermembrane space into the cytosol, leading to caspase activation and cell death. Because alterations in mitochondrial respiratory function, caspase activation and cell death with morphologic features compatible with apoptosis have been observed post mortem in the brain of patients with Parkinson's disease, we tried to clarify the potential role of Bax in this process in an immunohistochemical study on normal and Parkinson's disease post-mortem brain and primary mesencephalic cell cultures treated with MPP(+). We found that Bax is expressed ubiquitously by dopaminergic (DA) neurons in post-mortem brain of normal and Parkinson's disease subjects as well as in vitro. Using an antibody to Bax inserted into the outer mitochondrial membrane as an index of Bax activation, no significant differences were observed between control and Parkinson's disease subjects, regardless of the mesencephalic subregion analysed. However, in Parkinson's disease subjects, the percentage of Bax-positive melanized SNpc neurons containing Lewy bodies, suggestive of DA neuronal suffering, was significantly higher than the overall percentage of Bax-positive neurons among melanized neurons. Furthermore, all melanized SNpc neurons in Parkinson's disease subjects with activated caspase-3 were also immunoreactive for Bax, suggesting that Bax anchored in the outer mitochondrial membrane of melanized SNpc neurons showing signs of neuronal suffering or apoptosis is increased compared with DA neurons that are apparently unaltered. Surprisingly, MPP(+) treatment of tyrosine hydroxylase (TH)-positive neurons in primary mesencephalic cultures did not cause redistribution of Bax, although cytochrome c was released from the mitochondria and nuclear condensation/fragmentation was induced. Taken together, these findings suggest that in the human pathology, Bax may be a cofactor in caspase activation, but our in vitro data fail to indicate a central role for Bax in apoptotic death of DA neurons in an experimental Parkinson's disease paradigm.

1-Methyl-4-phenylpyridinium↗
PubMed2001

Noradrenaline provides long-term protection to dopaminergic neurons by reducing oxidative stress.

To better understand the neurotrophic function of the neurotransmitter noradrenaline, we have developed a model of mesencephalic cultures in which we find low concentrations (0.3-10 microM) of noradrenaline to be remarkably effective in promoting long-term survival and function of dopaminergic neurons. This protective action reproduced the effect of caspase inhibition. It was atypical in that it occurred independently of adrenoceptor activation and was mimicked by some antioxidants, redox metal chelators and the hydroxyl radical detoxifying enzyme catalase. Interestingly, intracellular reactive oxygen species (ROS) were drastically reduced by treatment with noradrenaline, indicating that the neurotransmitter itself acted as an antioxidant. Prevention of oxidative stress was, however, independent of the glutathione antioxidant defense system. Chemical analogues of noradrenaline bearing two free hydroxyl groups in the ortho position of the aromatic ring (o-catechols), as well as o-catechol itself, mimicked the survival promoting effects of the neurotransmitter, suggesting that this diphenolic structure was critical for both neuroprotection and reduction of ROS production. Paradoxically, the autoxidation of noradrenaline and the ensuing production of quinone metabolites may be required for both effects, as the neurotransmitter was spontaneously and rapidly degraded over time in the culture medium. These results support the concept that central noradrenergic mechanisms have a neuroprotective role, perhaps in part by reducing oxidative stress.

Animals↗
PubMed2001

[Prerequisites, indications and contraindications of IV-lysis of ischemic stroke with rt-PA].

BACKGROUND AND PURPOSE: To evaluate prerequisites, safety, and efficacy of i.v.-thrombolysis of ischemic stroke with rtPA in an academic medical center. METHODS: Over a period of 2 years and 10 months all patients admitted with a diagnosis of stroke were recruited. Inclusion and exclusion criteria for i.v.-thrombolysis were combined from large scale randomized controlled trials, the time window, however, could be extended up to 4 hours in subjects with a negative CT-scan. Prespecified outcome parameters were the modified Rankin Scale (mRS) and the Barthel Index (BI) at 3 months, and symptomatic hemorrhagic complications. Additionally, time parameters, such as onset-admission-time, door-Ct-time, door-needle time, and onset-needle time were recorded. RESULTS: During the reported period 103 patients underwent i.v.-thrombolysis, corresponding to 14.9% of all patients with ischemic stroke, and 47% of patients with ischemic stroke arriving in < 3 hours after symptom onset. The mean baseline NIHSS was 14, the mean mRS 13 (3-34), the mean age 70 (+/- 12) years. The following time intervals were observed: Onset-admission-time 64 min., door-CT-time 27 min., admission-needle-time 80 min., and onset-needle-time 142 min. There were 4 symptomatic intracerebral hemorrhagic transformations, including 3 parenchymal hemorrhages, 2 of them lethal, and one with almost full recovery. According to the mRS, 39% of patients had a good (mRS 0-1), 72% a good to moderate recovery (mRS 0-2). The corresponding figures for the BI were 60% BI 95-100 and 72% BI > 90. The mortality was 15%. CONCLUSION: The i.v.-thrombolysis of ischemic stroke with rt-PA demands appropriate organisation of the pre- and in-hospital phase and can be performed safely and efficaciously in daily clinical routine if inclusion and exclusion criteria as well as all safety measures during the critical phase after therapy are strictly obeyed.

Aged↗
PubMed2001

Design and application of new 16S rRNA-targeted oligonucleotide probes for the Azospirillum-Skermanella-Rhodocista-cluster.

The genera Azospirillum, Skermanella and Rhodocista form a phylogenetic subgroup within the alfa subclass of Proteobacteria. Based on comparative 16S rRNA sequence analysis a nested set of new oligonucleotide probes was designed. It comprises probes for the whole genus cluster Azospirillum-Skermanella-Rhodocista, for the Azospirilli subcluster I including A. lipoferum, A. doebereinerae, A. largimobile, A. brasilense and A. halopraeferens, for the Azospirilli subcluster II including A. amazonense, A. irakense and the genus Skermanella, for the genus Rhodocista as well as for all Azospirilli species or species cluster. The new probes allow a fast and reliable in situ identification of bacteria belonging to the Azospirillum-Skermanella-Rhodocista-cluster at different phylogenetic levels. The specificity of the new probes was tested with 56 strains of the Azospirillum-Rhodocista-Skermanella-cluster and selected reference cells from other genera by hybridising with the complete probe set. In addition, applications of the fluorescently labelled probes for in situ identification of isolates and for the in situ localisation of A. brasilense on maize roots were demonstrated using confocal laser scanning microscopy.

Alphaproteobacteria↗
PubMed2001

Automatic analysis of slides processed in the Comet assay.

In recent years the Comet assay (or single cell gel electrophoresis assay) has been established as a rapid and sensitive method for the detection of DNA damage. For early genotoxicity screening of new chemical entities in industrial toxicology, the Comet assay is more and more used for assessment of the DNA damaging potential of a test compound. In order to increase compound screening throughput, we have established an image analysis system for fully automated measurement of microscope slides processed in the Comet assay. For the comparative investigation various cell types, such as V79 Chinese hamster cells, mouse lymphoma cells and human leukocytes, were treated with several test compounds. Using tail moment as the quantitative parameter for comet formation, we show a very high correlation between our automatic image analysis system and a commercially available, interactive system (Comet Assay II of Perceptive Instruments). The possibility of analyzing 50 samples within 1 day and the high reproducibility of results make automated image processing a powerful tool for automatic analysis of slides processed in the Comet assay.

Animals↗
PubMed2001

Tapering off prednisolone and cyclosporin the first year after renal transplantation: the effect on glucose tolerance.

BACKGROUND: Glucose intolerance is an untoward side effect of some immunosuppressive and anti-hypertensive drugs. The primary aim of the present prospective observational study was to test the hypothesis that tapering off prednisolone and cyclosporin (CsA) the first year after transplantation may have beneficial effects on glucose tolerance in renal transplant recipients. METHODS: Ninety-one non-diabetic recipients were included, and 87 patients underwent a 75 g oral glucose tolerance test both 10 weeks and 1 year after renal transplantation. The change over time in 2-h blood glucose was compared with a number of variables potentially influencing glucose tolerance. RESULTS: The proportion of glucose intolerant recipients was reduced from 55 to 34% during the study. Univariate linear regression analysis showed a significant association between the reduction in daily prednisolone dose down to 5 mg and decline in blood glucose (P=0.001), whereas weight gain was associated with increasing blood glucose (P=0.031). Each 1-mg reduction of prednisolone dose leads to an estimated decline in 2-h blood glucose of 0.12 mmol/l based on the multiple linear regression model (P=0.003). Twelve out of 22 patients with post-transplant diabetes mellitus (PTDM) at baseline improved to normal or impaired glucose tolerance. Ten PTDM-subjects who remained diabetic 1 year after transplantation had lower serum insulin levels during the oral glucose challenge, and five patients treated with anti-diabetic drugs at baseline required hypoglycaemic drugs also at follow up. The decline in CsA level of 100 microg/l and the lower number of patients treated with beta-blockers at follow-up, did not alter glucose tolerance significantly. CONCLUSIONS: Tapering off prednisolone, but not CsA, significantly improves glucose tolerance during the first year after renal transplantation.

Adult↗
PubMed2001

Metabolic cardiovascular syndrome after renal transplantation.

BACKGROUND: Cardiovascular disease (CVD) is the major cause of death in renal transplant recipients. Traditional risk factors like hypertension, dyslipidaemia and diabetes mellitus are common, but cannot completely account for the high prevalence of CVD in this population. The aim of the present study was to assess whether post-transplant glucose intolerance, defined as post-transplant diabetes mellitus, impaired glucose tolerance, or impaired fasting glucose, is associated with metabolic disturbances known to increase risk of cardiovascular disease, similar to what has been observed in the general population. METHODS: One hundred and seventy-three consecutive patients were prospectively examined 10 weeks after transplantation. An oral glucose tolerance test was completed in 167 patients. Questionnaires, medical records, and the results of various blood tests were used to evaluate a number of known cardiovascular risk factors in all patients. RESULTS: Glucose intolerance was present in about one-half the recipients and was associated with age, a positive family history of ischaemic heart disease, acute rejection, higher levels of serum triglycerides, apolipoprotein B and 2-h insulin, and lower levels of serum HDL cholesterol. After adjustment for age and sex, lower HDL cholesterol (P=0.005), higher serum triglycerides (P<0.001), apolipoprotein B (P=0.039) and 2-h insulin (P<0.001) were still associated with post-transplant glucose intolerance. CONCLUSIONS: Ten weeks after renal transplantation glucose intolerance is associated with a clustering of cardiovascular risk factors and metabolic abnormalities, consistent with a post-transplant metabolic cardiovascular syndrome.

Adult↗