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G Michels

Publications and source records attributed to G Michels.

13 recordsLinked to original sources

Resveratrol induces apoptotic cell death in rat H4IIE hepatoma cells but necrosis in C6 glioma cells.

Resveratrol (trans-3,5,4',-trihydroxystilbene) is assumed to possess cancer-preventive and cancer-therapeutic properties. The aim of this project was to analyze cellular effects of resveratrol in metabolically active H4IIE rat hepatoma cells in comparison to metabolically poorly active C6 rat glioma cells. Resveratrol is rapidly taken up by both cell types and acts as a potent intracellular antioxidant. On the other hand, resveratrol in higher concentrations is relatively toxic to both cell lines as measured by the neutral red accumulation assay. In H4IIE cells, resveratrol concentrations rapidly decline to very low levels during the first hours of incubation due to formation of resveratrol glucuronides. The first resveratrol effect found at 3h after the start of resveratrol treatment was the induction of mild DNA damage as detected by the comet assay. Cell death was caused via induction of apoptosis as detected by caspase activation, oligonucleosomal DNA fragmentation and formation of apoptotic nuclei. Following DNA damage, resveratrol led to an activation of caspases 2 and 8/10 at 6h and consequently of caspase 3 at 12h, but failed to activate caspase 9. In contrast to H4IIE cells, resveratrol is not metabolised in C6 glioma cells and accumulates to concentrations which are assumed to drive the cell into necrosis. This suggests that the mode of cell death caused by resveratrol and the usefulness of resveratrol for cancer prevention and treatment critically depends on the metabolic capacity of the tumor cell to be eradicated.

Animals↗

[Levosimendan].

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3',5'-Cyclic-AMP Phosphodiesterases↗

[Everolimus].

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Everolimus↗

[Dilated cardiomyopathy in tachycardiac atrial flutter].

HISTORY AND CLINICAL FINDINGS: We present a 38-year-old male patient with progressive exertional dyspnoea and intermittent palpitations. The initial examination detected a regular tachycardia with a heart rate of 160 bpm. EXAMINATIONS, DIAGNOSIS: In association with intermittent palpitations the 12-lead ECG detected a typical type of atrial flutter. A transthoracic echocardiography and cardiac catheterization revealed a left ventricular dilation and marked systolic dysfunction (EF 39 %) with normal coronaries. The diagnosis of dilated cardiomyopathy was made on these findings. TREATMENT AND COURSE: On the basis of this diagnosis, we treated our patient by radiofrequency catheterablation, which successfully terminated atrial flutter. Three month after ablation the echocardiography was normal with an increase of the shortening fraction from 18 to 37 % and the patient was asymptomatic. Retrospectively the diagnosis of tachycardia-induced cardiomyopathy was made. CONCLUSION: Tachycardia-induced cardiomyopathy is a rare, but reversible form of dilated cardiomyopathy. The cornerstone in the management of these patients is to achieve a normal ventricular beating rate. Radiofrequency catheterablation is a curative therapeutic option that can terminate tachyarrhythmias and lead to significant improvement of left ventricular diameters, systolic function and symptoms in patients with tachycardia-induced cardiomyopathy.

Adult↗

Pro-apoptotic effects of the flavonoid luteolin in rat H4IIE cells.

Polyphenols are ubiquitous substances in the diet. Their anti-oxidative, anti-inflammatory and anti-viral effects are of interest for human health, and polyphenols such as luteolin are used at high concentrations in food supplements. The aim of this project was to determine the intrinsic effects of luteolin in H4IIE rat hepatoma cells. Luteolin is relatively toxic, cell death was caused via induction of apoptosis as detected by DNA-ladder formation, by nuclear fragmentation and activation of apoptotic enzymes (caspase-2, -3/7, -9 and -8/10). Luteolin (250 microM, 24 h) increased the caspase-3/7 activity four-fold and the caspase-9 activity six-fold. In a time course experiment caspase-9 is activated after 6h, while caspase-2 and -3/7 are activated after 12 h. After 24 h, caspase-8/10 also displays activation. We found a concentration-dependent increase in malondialdehyde release suggesting a prooxidative effect of luteolin. Furthermore, we analysed DNA strand break formation by luteolin and found a distinct increase of DNA strand breaks after incubation for 3h with 100 microM luteolin, a concentration which induces oligonucleosomal DNA cleavage at 24h. In conclusion, the sequence of events is compatible with the assumption that luteolin triggers the mitochondrial pathway of apoptosis, probably by inducing DNA damage.

Animals↗

[Recurrent syncope after blunt trauma of the thorax].

HISTORY AND ADMISSION FINDINGS: A 35-year-old patient presented with a non-penetrating chest trauma due to an automobile accident. Examinations showed a trauma of the left shoulder (reversed Hill-Sachs lesion). After diagnostic procedures, he underwent surgery four weeks later. During the hospital stay, the patient developed angina pectoris, dizziness and syncopes. INVESTIGATIONS AND DIAGNOSIS: When the patient was transferred to our institution a 12-leads electrocardiogram and blood analysis were unremarkable. Cardiac catheterization revealed a relaxation disorder of the left ventricular anterior wall with normal coronaries. The Holter-ECG detected with occasional attacks of dizziness and recurrent syncopes concurrent with intermittent episodes of high-degree atrioventricular block and supraventricular tachycardias. This led to the diagnosis of myocardial contusion with long term symptomatic arrhythmias. TREATMENT AND COURSE: Since syncopes and arrhythmias persisted over several weeks following myocardial contusion a combined therapy with a dual chamber pacemaker and beta-blocker was initiated. CONCLUSION: ECG monitoring after blunt chest trauma in the early period and after several days is mandatory to screen and prevent potentially life threatening posttraumatic arrhythmias.

Accidents, Traffic↗

The thiol reactivity of the oxidation product of 3,5,7-trihydroxy-4H-chromen-4-one containing flavonoids.

Flavonoids are assumed to have beneficial effects due to their antioxidant properties. The catechol moiety present in numerous flavonoids is oxidized during the antioxidative reaction yielding a quinone. Quinones are toxic due to their ability to react, e.g. with thiol groups. The 3,5,7-trihydroxy-4H-chromen-4-one group is another antioxidant pharmacophor in certain flavonoids. During the antioxidative reaction this group is also oxidized. The aim of the present study is to determine the thiol reactivity of this oxidized group. Galangin is a flavonoid that only contains the 3,5,7-trihydroxy-4H-chromen-4-one group as the antioxidant pharmacophor. Incubation of galangin with horseradish peroxidase/H(2)O(2) leads to an oxidation product which after addition of glutathione is instantaneously converted to an adduct. Based on these results it is expected that--similar to the catechol containing antioxidants--the 3,5,7-trihydroxy-4H-chromen-4-one containing antioxidants shift the damage provoked by oxidative stress from lipid peroxidation to thiol arylation. This should be considered in application of these types of antioxidants.

Animals↗

Colony establishment and maintenance of the eriophyid wheat curl mite Aceria tosichella for controlled transmission studies on a new virus-like pathogen.

High plains disease (HPD) is of serious economic concern for wheat and corn production, but little is known about the virus-like causal agent. In the field, HPD is often associated with Wheat streak mosaic virus (WSMV) and both pathogens are transmitted by the same eriophyid wheat curl mite, Aceria tosichella Keifer. The objective of this study was to develop methods for establishing and maintaining HPD-transmitting wheat curl mite colonies for their use in studies on HPD. Towards this goal, mite colonies from a mixed infection source were separated into colonies either (i). not viruliferous; (ii). only transmitting WSMV; or (iii). only transmitting HPD. Maintenance of these colonies required strictly separated incubator facilities and adaptation of mite-suitable transfer techniques to permit frequent passages of mites to healthy plants. The established colonies provided reliable sources of infective material to study the progression of HPD and/or WSMV in plants using sensitive immuno-detection assays. In conclusion, we have developed reliable methods with a poorly studied arthropod vector to examine the biology and properties of a new virus-like disease.

Animals↗

Organ culture of pig cornea: biochemical analyses of mid-term-stored corneal tissue.

Freshly prepared pig corneas were cultured at 22 degrees C in TC 199 medium supplemented with HEPES buffer, antibiotics and 10% sterile pig blood serum. The cultures were maintained in a closed system up to 30 days. The hydration as measured by wet and dry weights increased from 80 to 94% after 2 weeks of storage. Glucose decreased slowly and continuously during the culture time by 0.32 mmol in 30 days. This was equivalent to 11 mumol/day, 0.46 mumol/h and finally 0.264 mumol/h/cm2. Lactate increased in the culture accordingly by 0.34 mumol/h/cm2. In the corneal epithelium of the cultured tissues the glucose levels--normally at about 5 mumol/g--equilibrated with those of the medium during the first 10 days; later the epithelial glucose levels increased up to 20-30 mumol/g. The glycogen content of the epithelium remained constant for the first 10 days of storage. The ATP/ADP ratios in the corneal epithelium initially decreased but later recovered to values of about 12. The pO2 in the culture system decreased from 156 to 120 mm Hg, which is equivalent to an oxygen consumption of 7.41 microliters O2/h/cm2. The CO2 production initiating from a level of 16.6 mm Hg was 4.88 microliters/h/cm2. The data showed that the cornea was viable in this culture system for 30 days.

Animals↗