Are insulin resistance and atherosclerosis the consequences of oxidative stress?
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Adenosine Triphosphate↗
Biomedical subjects
I Wittmann
Publications and source records attributed to I Wittmann.
Redox agents modulate a(K+)0 changes evoked by acetylcholine and adrenaline in frog heart.
It was observed earlier, that in the presence of oxidizing agents the acetylcholine exerted a positive ino- and chronotropic effect, while the positive ino- and chronotropic action of adrenaline was decreased. In the presence of reducing agents both the negative inotropic effect of acetylcholine and the positive inotropic action of adrenaline was increased. Analyzing the ionic mechanism background of these correlations, the changes of extracellular K(+)-activity (a(K+)0) were followed and it was established that; In relation to slow transient changes (in min time ranges) an oxidant decreased the a(K+)0 following acetylcholine, while it increased the a(K+)0 after adrenaline application. A reductant increased the a(K+)0 with acetylcholine, but decreased a(K+)0 in the presence of adrenaline. Because of the inverse character of redox modulation on a(K+)0 levels, a reverse change in a(K+)0 should be (at least one of) the site of action of the opposite effects of oxidants or reductants exerted on ino- and chronotropism of acetylcholine or adrenaline.
Acetylcholine↗
Free radicals and their interpretations.
Oxygen free radicals can be blamed for evoking gastric mucosal damage, because of the protective effect of some lipid soluble free radical scavengers (vitamin A related compounds, Vitamin E). Direct determination of free oxygen radicals related chemical entities in the gastric tissue during ulcerogenesis yielded controversial results. Aluminum antacid compound together with acid binding property exhibited cytoprotection too, elevating the tissue PGE2 level substantially. Magnesium containing antacid according to our model experiments on red blood cells damage by free radicals, is capable to bind free radicals as well as to counteract with the dangerous intracellular calcium accumulation. It has been concluded that aluminum-magnesium antacid has a cytoprotective effect via: 1. acid binding; 2. prostaglandin generation; 3. free radical scavenging; 4. calcium antagonist activity.
Aluminum Hydroxide↗
Effect of ionic milieu to the free radicals generated by phenizine methosulphate (PMS).
The effect of free radicals generated by PMS was studied for membrane damage in the presence of different ions in the erythrocyte model. The degree of membrane damage depended on the quality of ionic composition in the incubation medium. We supposed that the degree of membrane damage depends on the average life and concentration and/or reactivity of the free radicals generated. For control of this supposition free radicals were generated by PMS in the presence of Sodium-di-thionite in isosmotic, waterly systems with different ionic composition. At different time intervals the concentration of free radicals was measured by the ESR method. It seams that concentration of radicals depends on the qualitative composition of ionic milieu. The increase of the average life of free radicals generated by PMS is accompanied by decrease in their reactivity. This is reflected by a moderate membrane damage.
Electron Spin Resonance Spectroscopy↗
In vitro method for measurement of free radical effects: effect of PMS (phenazine methosulphate) on red blood cell membrane.
The aim of this study was to elaborate a simple in vitro model for rapid and quantitative measurement of free radical effects. Free radical generating characteristics of PMS were measured in the case of red blood cell (RBC) membrane. The mechanism of free radical action was investigated in MgCl2, CaCl2, BaCl2 and in Verapamil HCl medium. The most important result of the investigations is as follows: Membrane damage of RBC provoked by the mechanism of free radical generation of PMS is proportional to the intracellular K+-efflux and to the extracellular Na+-influx. The PMS dependent K+-efflux in a NaCl containing medium in the presence of CaCl2 increases significantly, while it remains unchanged in MgCl2 medium. The PMS dependent K+-efflux and Na+-influx were considerably decreased by Verapamil HCl in NaCl containing solution. We have come to the conclusion that new, non-selective pores are formed in the membrane. The measure of the damage increases in the presence of Ca2+ions and decreases in the medium containing Verapamil HCl.
Barium↗
Changes in autorhythmic heart frequency elicited by redox agents.
In isolated frog heart it was established that methylene-blue (MB, an oxidizing agent) decreased, while ascorbate (ASC, a reducing agent) increased the frequency of autorhythmic heart contractions. After MB treatment, in parallel with this phenomenon, the extracellular K+ concentration [K+]o showed a slow increase, but following ASC application a slow decrease occurred. Since these correlations are in good accordance with the idea that the pacemaking ability of heart, among other properties, depends on the voltage and time-dependent decrease in potassium conductance following the spike, changes in [K+]o might be one mechanism by which oxidizing and reducing agents modulate heart frequencies. On the basis of the effect of insulin (INS) and K-strophantoside (STR) on these modulatory influences, it is presumed that the changes in slow delta [K+]o transients might result, at least partly, from the effect of redox agents on the active transport system. In light of the increase in passive K+ fluxes after oxidant treatment and the decrease in this parameter following reductant treatment an effect of redox agents on the characteristics of the K+-channel is also postulated.
Animals↗
The influence of phenobarbital on the pharmacokinetics of propranolol in pregnancy.
In 7 pregnant hypertensive patients the elimination half-life of propranolol was enhanced to 6.1 +/- 1.2 h in comparison to 4.4 +/- 0.4 in 9 nonpregnant females. In 8 out of 11 pregnant hypertensive patients in the 29th week of gestation treated with 90 mg phenobarbital daily for at least 7 days before starting propranolol therapy, the half-life of propranolol was 3.1 +/- 0.4 h only. This significant difference between pregnant women with and without phenobarbital pretreatment is discussed as enzyme induction by phenobarbital.
Drug Interactions↗
Inverse modulation of extracellular Na+- and K+-activities by ascorbate or methylene blue.
On analyzing the mechanisms of the internal environment type redox regulation of physiological processes it was observed on frog rectus muscles that during acetylcholine contractures methylene blue pretreatment inhibited, but ascorbate pretreatment enhanced the slow transient changes of extracellular Na+-activity. At the same time, these modifications were inverse for K+-transients. Because k-strophantoside was capable of influencing these effects radically it seems highly plausible to assume that the principal site of action of these modulations is the inhibitory impact of methylene blue, while the enhancing effect of ascorbate on (Na+ + K+)-ATPase may likely be explained on redox basis.
Animals↗
Redox state potential influences (+/-) delta [Na+]o activity values during acetylcholine contractures of frog skeletal muscles.
1. The slow alterations in the activity of extracellular Na+ concentrations were measured by using ion-selective electrodes. 2. In the first min there is an increase in the changes of the activity of extracellular Na+ following acetylcholine evoked contractures. 3. This increment was significantly inhibited by k-Strophantoside application, suggesting an active transport origin of this first peak. 4. In the second min a strong decrease in the activity of extracellular Na+ concentration followed. 5. Reducing agent (ascorbate) increased, while oxidant (methylene-blue) decreased both the first increment and the sequential decrement in the activity of the extracellular Na+ concentrations. 6. On the basis of these experiments a site of action of the redox regulation of excitatory processes could be the modification of Na+ fluxes.
Acetylcholine↗
Relationship between the tissue redox state potential and dak/dt changes of [K+]0 activity during k-strophantoside or acetylcholine induced contractures.
It was established that oxidosis evoked by methylene blue during k-strophantoside and acetylcholine contractures in skeletal muscle was accompanied by an increase in the changes of [K+]0 activity, while redosis evoked by ascorbate under the same conditions was accompanied by a decrease in the changes of [K+]0 activity. These changes in [K+]0 activity parallelled the alterations of contractures caused by oxidosis or redosis suggesting that changes in the [K+]0 transient play an important role in these phenomena.
Acetylcholine↗
A case of aortic valve disease associated with Tropheryma whippelii infection in the absence of other signs of Whipple's disease.
A case of endocarditis caused by Tropheryma whippelii is reported. The 69-year-old patient was diagnosed as suffering from severe aortic regurgitation requiring aortic valve replacement, but showed no other symptoms of Whipple's disease. T. whippelii was detected in the explanted aortic valve by broad-range PCR amplification of the 16S rDNA and subsequent sequence analysis of the product. The etiologic agent was classified as a type 2A sequence variant based on the 16S-23S intergenic spacer and the 23S rDNA (domain III) sequences. The histological examination of the aortic valve was compatible with Whipple's disease. A duodenal biopsy revealed an infection with Giardia lamblia, but T. whippelii and histological signs of Whipple's disease were not detectable.
Actinobacteria↗
Prevalence, course and risk factors of diabetic nephropathy in type-2 diabetes mellitus.
UNLABELLED: Contrary to the well-known features of diabetic nephropathy (DNP) in type-1 diabetic patients (pts), the prevalence, course and risk factors of DNP in in type-2 diabetic pts are not clear. The aim of the present study was to assess the prevalence of microalbuminuria (MA) and macroalbuminuria (MAA), their relationship with other diabetic complications and with some known cardiovascular risk factors in 200 in type-2 diabetic pts (100 females and 100 males). 68 pts (33%) were normalbuminuric (NA), 55 (27.5%) had MA and 77 (38.5%) had MAA. There was no significant difference among these three groups in age, BMI or the time actually elapsed since the diabetes and hypertension were diagnosed. BMI was high in each group (28.8 +/- 5.29, 28.0 +/- 5.2 and 29.8 +/- 4.6 kg/m2 mean +/- SD). 65% of pts with NA, 77% of those with MA and 81% of pts with MAA had hypertension. MAA pts were more frequently smokers and former smokers, than MA and NA pts (56% vs 32% and 22%). Average GRF values (ml/min/1.73 m2) were 71.9 +/- 26.8 in NA pts, 82.3 +/- 36.8 in MA pts and 56.3 +/- 32 in MAA pts. There was no significant correlation between the urinary albumin excretion (UAE) and glycemic control, serum (se) cholesterol and se HDL cholesterol. At the same time UAE showed a significant positive correlation with se trigliceride (P < 0.01), se uric acid (P < 0.01) and se creatinine (P < 0.01) while a significant negative correlation was found with GFR (P < 0.01). Diabetic non-proliferative retinopathy (RP) was detected even in NA pts (27%) while 51% of MAA pts were without RP. 56% of NA pts, 57% of MA pts and 93% of MAA pts had macroangiopathy. CONCLUSIONS: (1) renal function can be impaired even in type-2 diabetic pts with NA and MA, (2) well-known cardiovascular risk factors seem to have a close relation with renal damage in type-2 diabetes (3) renal lesions in type-2 diabetic pts may be caused by diseases other than diabetes (e.g. arteriosclerosis, hypertension) (4) unlike in type-1 diabetes, where the strict glycemic control is the main preventive factor of DNP, in type-2 diabetes, the control of hypertension, hyperlipidemia, obesity, hyperuricemia may have priority.
Adult↗