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  • Phenylketonuria  (6)
  • Lactate  (3)
  • SITS  (3)
  • 1
    Digitale Medien
    Digitale Medien
    Springer
    Pflügers Archiv 389 (1981), S. 271-275 
    ISSN: 1432-2013
    Schlagwort(e): Adaptation, HCO 3 − transport ; Glycodiazine transport ; Metabolic acidosis ; Metabolic alkalosis ; Acetazolamide ; SITS ; Potassium deficiency
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Using the technique of capillary perfusion and simultaneous luminal stop flow microperfusion the reabsorption of bicarbonate and glycodiazine from the papillary collecting duct was evaluated. Starting with equal H14CO 3 − and3H-glycodiazine concentrations in the luminal and peritubular perfusates, the decrease in the luminal concentration at 10 and 45 s contact time was measured. In control rats with 25 mmol/l HCO 3 − in the perfusates the rate of HCO 3 − reabsorption calculated from the 10 s values was 0.34 nmol cm−2s−1. In acute metabolic acidosis, the rate of bicarbonate reabsorption was 2,3 times higher. In metabolic alkalosis, the rate of bicarbonate absorption dropped to 13% of the control values. Also the 45 s values of acidotic and alkalotic animals differed significantly from each other. With 25 mmol/l glycodiazine in both perfusates the rate of biffer reabsorption as calculated from the 10 s values was 0.76 nmol cm−2s−1 in control rats and did not deviate significantly from this value in acidotic and alkalotic animals. In control rats the bicarbonate reabsorption in % was the same, no matter whether both luminal and capillary perfusate contained 25 mmol/l bicarbonate or 10 mmol/l. In acidotic rats the rate of HCO 3 − reabsorption did not change significantly if all Na+ in the perfusates was replaced by choline (0.88 versus 0.79 nmol cm−2s−1 at 25 mmol/l HCO 3 − ). When in acidotic rats 0.1 mmol/l acetazolamide or 1 mmol/l SITS (4-acetamido-4′-isothiocyanatostilbene-2,2′-disulfonic acid) was added to both perfusates the rate of HCO 3 − reabsorption dropped by 75 and 58%, respectively. A potassium deficient diet for one week and DOCA administration had no influence on the bicarbonate reabsorption of rats which were on standard diet. The data indicate that (1) the buffer reabsorption from the papillary collecting duct is rather due to H+ ion secretion than to buffer anion reabsorption. (2) The adaptation to metabolic acidosis and alkalosis is specific for bicarbonate and not seen with glycodiazine. (3) Within the concentration range tested the HCO 3 − reabsorption rises linearly with the HCO 3 t- concentration. (4) The HCO 3 − reabsorption in the papillary collecting duct is Na+-independent, it can be inhibited by acetazolamide and SITS, but is not influenced by K+-deficient diet plus DOCA.
    Materialart: Digitale Medien
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  • 2
    Digitale Medien
    Digitale Medien
    Springer
    Pflügers Archiv 407 (1986), S. 488-492 
    ISSN: 1432-2013
    Schlagwort(e): Lactate ; Pyruvate ; 3-hydroxybutyrate ; Acetoacetate ; Nonspecific anion channel
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract In order to study the characteristic of contraluminal transport of hydrophylic small fatty acids the in situ stopped flow microperfusion technique [12] has been applied. By measuring with 4 s contact time the decrease in the contraluminal concentration of the respective radiolabelled substances the concentration dependence of the influx into the cortical cells was tested. The 4 s decrease in contraluminal concentration of chloroacetate,l-lactate,d-lactate, 3-hydroxybutyrate and acetoacetate was between 26% and 31%. For each substance the percent decrease was the same, no matter whether it was offered in a concentration of 0.1 or 10 mmol/l. Contraluminal disappearance of 0.1 mmol/ll-lactate was not influenced by 5 mmol/l H2DIDS, probenecid, phloretin, mersalyl or cyanocinnamate, but it was significantly (37%) inhibited by 5-nitro-2-(phenyl-propyl-amino) benzoate, a blocker of the nonspecific anion channel. The percent decrease in propionate uptake was somewhat larger — between 36% and 39% — but again not different at 0.01, 0.1, 1.0 and 10 mmol/l. With pyruvate the contraluminal decrease was 20% at 0.1 mmol/l and 31% at 10 mmol/l. The percent disappearance of the aromatic pyrazinoate was 38% and 34% at 0.1 and 10 mmol/l and for nicotinate 42% and 22%, respectively. The disappearance of nicotinate (0.1 mmol/l) was significantly inhibited by 10 mmol/l pyrazinoate and paraaminohippurate (PAH). The data are in agreement with the hypothesis that the hydrophilic small fatty acids traverse the contraluminal cell side by simple diffusion, possibly via the unspecific anion channel [14], pyruvate via the dicarboxylic acid pathway in a cooperative manner and pyrazinoate, as well as nicotinate, via the PAH pathway.
    Materialart: Digitale Medien
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  • 3
    Digitale Medien
    Digitale Medien
    Springer
    Pflügers Archiv 368 (1977), S. 245-252 
    ISSN: 1432-2013
    Schlagwort(e): Renal tubule ; H+ ion secretion ; Na+ coupled transport ; Ouabain ; SITS
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The rate of active transport by the proximal renal tubule of amino acid (l-histidine), sugar (α-methyl-d-glycoside), H+ ions (glycodiazine), phosphate and para-aminohippurate was evaluated by measuring the zero net flux concentration difference (Δc) of these substances. In the case of calcium the electrochemical potential differenceΔc +zFci Δϕ/RT) was the criterion employed. The rate of isotonic Na+-absorption (JNa) was measured with the shrinking droplet method. The effect of ouabain on the transport of these substances was tested in the golden hamster and the effect of SITS (4-acetamido-4′isothiocyanatostilbene 2,2′-disulfonic acid) was observed in rats. Ouabain (1 mM) applied peritubularly incompletely inhibited JNa (80%), but in combination with acetazolamide (0.2 mM) the inhibition was almost complete (93%). In addition, ouabain inhibited the sodium coupled (secondary active) transport processes ofl-histidine, α-methyl-d-glycoside, calcium and phosphate by more than 75%. It did not affect H+ (glycodiazine) transport and PAH transport was only slightly affected. When SITS (1 mM) was applied from both sides of the cell it inhibited H+ (glycodiazine) transport by 72% and reduced JNa by 38% when given from only the peritubular cell side. SITS (1 mM), however, had no significant affect on H+ secretion and sodium reabsorption if it was applied from only the luminal side. Furthermore it had no affect on the other transport processes tested, regardless of the cell side to which it was applied. When the HCO 3 − buffer or physically related buffers were omitted from the perfusate the absorption of Na+ was reduced by 66%, phosphate by 44%, andl-histidine by 15%. All the other transport processes tested were not significantly affected. The data are consistent with the hypothesis that the active transport processes of histidine, α-methyl-d-glycoside and phosphate, which are located in the brush border, are driven by a sodium gradient which is abolished by ouabain. This may also apply to the Na+-Ca2+ countertransport located at the contraluminal cell side. The residual Na+ transport remaining in the presence of ouabain is likely to be passively driven by the continuing H+ transport which probably is driven directly by ATP. SITS seems to inhibit the exit step of HCO 3 − from the cell and secondary to that, the luminal H+-Na+ exchange and consequently the Na+ reabsorption. In the absence of HCO 3 − buffer in the perfusates the luminal H+-Na+ exchange seems to be affected and the pattern of inhibition of the other transport processes is almost the same as with SITS. The different effects onP i reabsorption observed under these conditions might be explained by possible variations in intracellular pH.
    Materialart: Digitale Medien
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  • 4
    Digitale Medien
    Digitale Medien
    Springer
    Pflügers Archiv 395 (1982), S. 212-219 
    ISSN: 1432-2013
    Schlagwort(e): SITS ; Probenecid ; Phloretin ; Acetazolamide ; Lactate ; Renal tubule
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The transport ofd-lactate across the epithelium of the late proximal convolution was investigated by two methods: 1. by measuring the zero net flux transtubular concentration difference (Δc tt,45s) and the permeability (P) ofd-lactate and calculating from both the transtubular active transport rate (J lac act ). 2. By measuring the 3.5 s efflux ofd-lactate from the tubular lumen, while blood was flowing through the capillaries. The 3.5 s efflux comprises two components, one going through the brush border (J lac bb ) and one going the paracellular pathway (J lac paracell =P lac·c lac lumen). Both,J lac act andJ lac bb ofd-lactate gave the sameK m 1.9 and 1.7 mmol/l and the same maximal transport rate 3.2 and 2.9 pmol cm−1 s−1. TheK i ofl-lactate tested againstJ lac act andJ lac bb ofd-lactate was also the same: 1.1 and 1.0 mmol/l. These data indicate that under our experimental conditions only the flux through the brush border seems to be rate limiting and thatd-lactate uses the same transport system asl-lactate. When Na+ was omitted from the perfusatesJ lac act disappeared completely, whileJ lac bb was reduced by 64%. These data reflect the Na+ dependence of thed-lactate transport through the brush border. Variation of intra-and extracellular pH by raisingpCO2, omitting HCO 3 − from the perfusates or adding acetazolamide had no effect on the transport ofd-lactate when α-ketoglutarate was used as fuel. However, when acetate was used as fuel, intracellular acidosis brought the reducedJ lac act back to the values obtained with α-ketoglutarate as fuel. It is suggested that this is an effect on a contraluminal transport step. Probenecid (5 mmol/l) and phloretin (0.25 mmol/l) inhibitedJ lac act significantly.J lac bb , however, was only inhibited by probenecid when acetate was used as fuel. These data indicate that both compounds act on thed-lactate exit at the contraluminal cell side, but that probenecid acts in addition at the luminal cell side. SITS (1 mmol/l) augmentedJ lac bb when acetate was used as fuel and is similar to the effect of lowering intracellular pH as described above. The SH reagents mersalyl (1.0 mmol/l) and maleolylglycine (1 mmol/l) did not influenceJ lac bb .
    Materialart: Digitale Medien
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  • 5
    ISSN: 1432-1076
    Schlagwort(e): Phenylketonuria ; Carnitine ; Iron ; Ferritin
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract A previous observation of decreased serum carnitine concentrations in phenylketonuria (PKU) was investigated in 169 patients either on a strict diet (n=107; median: 8.1 years) or off diet (n=62; median: 15.0 years). Fifty-seven metabolically healthy children (median: 8.5 years) served as controls. PKU patients on a strict diet and older than 2 years had significantly lower serum carnitine concentrations (19.4±5.4 μmol/l) than those off diet (29.6±6.7 μmol/l). PKU patients on diet also had significantly lower concentrations of haemoglobin and serum ferritin than those off diet. A linear correlation existed between total serum carnitine and ferritin concentrations up to 40 μg/l (r=0.52;P〈0.01). As iron is an essential cofactor of carnitine synthesis we conclude that reduced endogenous carnitine synthesis due to an inadequate availability of iron may be a major cause of low serum carnitine concentrations. The low carnitine content of the strict and highly protein-reduced diet additionally contributes to a decrease in the serum carnitine concentration. Our results show that a further optimization of the PKU diet increasing either iron availability or carnitine intake should be considered.
    Materialart: Digitale Medien
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  • 6
    Digitale Medien
    Digitale Medien
    Springer
    European journal of pediatrics 149 (1990), S. 13-16 
    ISSN: 1432-1076
    Schlagwort(e): Phenylketonuria ; Phenylalanine intake ; Diet control ; Compliance
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The daily Phe intakes of normally growing 1- to 6-year-old treated PKU patients were evaluated. The children received protein in amounts that varied from 2.26±0.47 g/kg body weight per day (mean±SD) at the age of 6 to 1.81±0.35 at the age of 72 months. Mean Phe intakes declining from 34±7 at the age of 6 months to 15±5 mg/kg body weight per day at the age of 72 months were required to maintain mean median plasma Phe levels around 6.0 mg/dl.
    Materialart: Digitale Medien
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  • 7
    Digitale Medien
    Digitale Medien
    Springer
    European journal of pediatrics 155 (1996), S. S64 
    ISSN: 1432-1076
    Schlagwort(e): Key words Hyperphenylaninaemia ; Phenylketonuria ; Evoked potentials ; Metabolic disorders ; Dopamine
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract We performed studies of multimodal evoked potentials and peripheral sensory and motor nerve conductions in 33 early and 6 late treated patients with phenylketonuria. The studies revealed the following picture: 1. In 27% of early treated patients latencies of visual evoked potentials were increased. The cause for these changes is unknown. 2. Nerve conduction studies showed the presence of a minor sensory neuropathy which in rare cases may also affect peripheral motor nerves. This neuropathy did not have features of a central-peripheral distal axonopathy which argues against a toxic/nutritional causation. 3. Deficits in the central sensory, motor, and auditory pathways were present, but rare in early treated patients. If the results of electrophysiological studies reported by different groups are compared, the emerging picture is very similar and the majority of the – minor – differences is likely to be explained by technical aspects.
    Materialart: Digitale Medien
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  • 8
    ISSN: 1432-1076
    Schlagwort(e): Phenylketonuria ; Adolescents ; Magnetic resonance imaging ; Myelination
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Cranial magnetic resonance imaging (MRI) was performed in nine treated adolescents with hyperphenylalaninaemia (HPA) in order to analyse possible changes in myelination. Three patients suffered from type I HPA, four from type II and two from type III (persistent HPA). Images were obtained with a 1.5T unit using spin-echo-sequences. In all patients with type I or type II HPA, abnormal findings in the cerebral white matter were demonstrated including band-like and/or confluent patchy areas of high signal intensity predominantly in the peritrigonal region, with anterior and posterior periventricular extension and/or involvement of the subcortical white matter. The extent of MRI changes did not correlate with the initiation, duration or quality of dietary treatment. There was also no consistent relationship between electrophysiological changes and white matter abnormalities on MRI. Our findings suggest a disturbance of myelination in patients with treated HPA. These results correspond well with earlier neuropathological and biochemical studies in untreated patients.
    Materialart: Digitale Medien
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  • 9
    ISSN: 1432-1076
    Schlagwort(e): Phenylketonuria ; Myelination ; Magnetic resonance imaging ; 1H spectroscopy ; T2 relaxometry
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract In order to further clarify the pathogenesis and clinical significance of MRI white matter abnormalities in treated hyperphenylalaninaemia (HPA), ten patients (seven type I HPA, two type II and one type III) underwent T2 relaxometry (n=8) and/or1H spectroscopy (n=7) in addition to conventional MR spin-echo imaging at 1.5 T. Two patients with severe MRI abnormalities had repeat examinations during and after a 6-to 8-month period of strict diet control. The clinical evaluation included a detailed neurological examination. In nine out of ten patients visual evoked potentials (VEP) were obtained parallel to the MR examination. MR imaging demonstrated typical symmetrical areas of prolonged T2 relaxation time predominantly in the posterior periventricular white matter in all but one of type I and II patients. There was no consistent relationship between MRI findings and time of diagnosis/initiation of therapy, IQ or visual evoked potential changes. MRI abnormalities tended to be more severe in patients with poor dietary control and high current plasma phenylalanine levels, whereas a normal MRI was found only in patients with plasma phenylalanine levels continuously below 0.36 mmol/l. There was marked regression of MRI abnormalities already after 3 months of strict diet control. T2 relaxometry showed a bi-exponential behaviour of T2 in the affected white matter, with a slow component of about 200–450 ms, indicating an increase in free (extracellular) water.1H spectroscopy revealed no signs of severe neuronal damage. We conclude, that the observed white matter changes in treated HPA probably represent reversible structural myelin changes rather than permanent demyelination.
    Materialart: Digitale Medien
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  • 10
    ISSN: 1432-1076
    Schlagwort(e): Phenylketonuria ; Selective ; sustained attention ; Impaired frontal lobe functions
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Twenty normally intelligent children with early treated phenylketonuria (PKU) (IQ: mean=101.4, SD=10.0; age: mean=10 years 11 months, SD=1.3 years) and 20 healthy controls, matched for age, sex and IQ, were assessed for their selective (Stroop Task) and sustained attention (Test-d-2). Using positron emission tomography an activation of the frontal lobe during the Stroop task had previously been demonstrated. In addition to the Stroop Task and the Test-d-2, a short-term memory test as a “non-frontal-lobe-function-task” was administered to all subjects. Group comparisons demonstrated that PKU children had specific deficits in selective and sustained attention, which were significantly correlated with the concurrent serum phenylalanine concentration. Conclusion The results give evidence that even dietary treated children with PKU were suffering from impaired attentional control mechanisms in spite of a normal IQ. The deficits might be the result of impaired frontal lobe functions.
    Materialart: Digitale Medien
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