The amiloride-inhibitable Na+ conductance is reduced by the cystic fibrosis transmembrane conductance regulator in normal but not in cystic fibrosis airways.

Cystic fibrosis (CF) airway cells, besides their well-known defect in cAMP-dependent Cl- conductance, are characterized by an enhanced Na+ conductance. In this study we have examined the Na+ conductance in human respiratory tract by measuring transepithelial voltage and resistance (Vte, Rte) and by assessing membrane voltages (Vm) of freshly isolated airway epithelial cells from CF and non-CF patients. Basal amiloride inhibitable (10 micromol/liter) equivalent short circuit current (Isc = Vte/Rte) was significantly increased in CF compared with non-CF tissues. After stimulation by forskolin (10 micromol/liter) a significant depolarization of Vm corresponding to the cAMP-dependent activation of a Cl- conductance was observed in non-CF but not in CF airway cells. In non-CF tissue but not in CF tissue the effects of amiloride and N-methyl-D-glucamine on Vm were attenuated in the presence of forskolin. Also the amiloride-inhibitable Isc was significantly reduced by forskolin (1 micromol/liter) and isobutylmethylxanthine (IBMX; 100 micromol/liter) only in non-CF tissue. We conclude that cystic fibrosis transmembrane conductance regulator acts as a downregulator of epithelial Na+ channels in human airways. This downregulation of epithelial Na+ channels is absent in CF airways, leading to hyperabsorption and to the characteristic increase in mucus viscosity.     

Magnetic resonance imaging as a tool to image neuroinflammation in a rat model of Parkinson's disease – phagocyte influx to the brain is promoted by bilberry‐enriched diet

Neuroinflammation is a chronic event in neurodegenerative disorders. In the rat model of Parkinson's disease, including a striatal injection of the neurotoxin 6‐hydroxydopamine (6‐OHDA), antioxidant treatment affects the inflammatory process. Despite a heavy accumulation of microglia early after the injury, dopamine nerve fibre regeneration occurs. It remains unclear why this heavy accumulation of microglia is found early after the lesion in antioxidant‐treated animals, or even more, what is the origin of these microglia. In this study magnetic resonance imaging (MRI) was used to elucidate whether the inflammatory response was generated from the blood or from activated brain microglia. Superparamagnetic iron oxide (SPIO) nanoparticles were injected intravenously prior to a striatal 6‐OHDA injection to tag phagocytes in the blood. Rats were fed either with bilberry‐enriched or control diet. T2*‐weighted MRI scans were performed 1 week after the lesion, and hypointense areas were calculated from T2*‐weighted images, to monitor the presence of SPIO particles. The results revealed that feeding the animals with bilberries significantly promoted accumulation of blood‐derived immune cells. Gadolinium‐enhanced MRI demonstrated no difference in leakage of the blood–brain barrier independent of diets. To conclude, bilberry‐enriched diet promotes an influx of periphery‐derived immune cells to the brain early after injury.     

Biofeedback training in patients with fecal incontinence

PURPOSE: This study was undertaken to assess the functional results of biofeedback training in patients with fecal incontinence in relation to clinical presentation and anorectal manometry results. METHODS: Twenty-six consecutive patients with fecal incontinence were treated with biofeedback training using anorectal manometry pressure for visual feedback. Ten patients had passive incontinence only, six patients had urge incontinence, and ten patients had combined passive and urge incontinence. RESULTS: Patients with urge incontinence had a lower maximum voluntary contraction pressure (92 ± 12 mmHg) and lower maximum tolerable volume (78 ± 13 ml) than patients with passive incontinence (140 ± 43 mmHg and 166 ± 73 ml). Twenty-two patients completed the treatment, five patients (23 percent) showed excellent improvement, nine patients (41 percent) had good results, and eight (36 percent) patients showed no improvement. At follow-up on average of 21 months after therapy, 41 percent of our patients reported continued improvement. The maximum tolerable volume was higher in those with excellent (140.4 ± 6.8 ml) or good (156.3 ± 6.64 ml) results of therapy than it was in those with poor results (88.5 ± 2.5 ml). Greater asymmetry of the anal sphincter also correlated to poor results. CONCLUSION: Biofeedback therapy improved continence immediately after training and at follow-up after 21 months, but the initial results were better. The urge fecal incontinence seems to be related to function of the external anal sphincter and to the maximum tolerable volume. Low maximum tolerable volume and anal sphincter asymmetry were associated with a poor outcome of therapy     

Erythroid response to treatment with G-CSF plus erythropoietin for the anaemia of patients with myelodysplastic syndromes: proposal for a predictive model

Previous studies have shown that approximately 40% of patients with myelodysplastic syndrome (MDS) and anaemia respond to treatment with human recombinant granulocyte-CSF (G-CSF) plus erythropoietin (epo). The present study was designed to investigate pre-treatment variables for their ability to predict erythroid responses to this treatment. 98 patients with MDS (30 RA, 31 RARS, 32 RAEB, five RAEB-t) were treated with a combination of G-CSF (0.3–3.0 μg/kg/d, s.c.) and epo (60–300 U/kg/d, s.c.) for at least 10 weeks. Minimum criteria for erythroid response was a 100% reduction of red blood cell (RBC) transfusion need or an increase in haemoglobin level of  1.5 g/dl. 35 patients (36%) showed responses to treatment. Medium duration of response was 11–24 months. In multivariate analysis, serum erythropoietin levels and initial RBC-transfusion need retained high statistical significance ( P  < 0.01). Using pre-treatment serum epo levels as a ternary variable (< 100, 100–500 or > 500 U/l) and RBC transfusion need as a binary variable (< 2 or  2 units per month), the analysis provided a predictive score for erythroid response. This score divided patients into three groups: one group with a high probability of erythroid responses (74%), one intermediate group (23%) and one group with poor responses to treatment (7%). This predictive scoring system could be used in decisions regarding use of these cytokines for treating the anaemia of MDS, both for defining patients who should not be given the treatment and for selecting patients for inclusion in prospective trials.     

Dietary habits of adolescent females

The dietary intakes of 178 females (mean age was 12.8 ± 0.1 (S.E.M.)) were determined through 24‐hour diet recalls in both the fall and spring of one school year. The average subject consumed less than the recommended number of servings of three of the Basic Four food groups. Dietary intake at all meals but lunch, were similar in the fall and spring. Differences in the dietary intake at lunch may have occurred because fewer girls selected National School Lunch Program's Type A lunches in the spring than in the fall. Subjects who did select Type A lunches consumed more servings from the Basic Four groups than those subjects eating a la carte items or sack lunches. Subjects who selected Type A school lunches were significantly younger than those who selected d la carte items. Ninety percent of the subjects snacked at least once during the day. About half of the food consumed during snacks could not be classified as being representative of any of the Basic Four food groups.     

Calcium supplements and milk: effects on acid-base balance and on retention of calcium, magnesium, and phosphorus

The effect of supplementing a basal diet containing 697 mg calcium daily (17.4 mmol/d) with an additional 900 mg Ca daily from milk, Ca chloride, or a Ca carbonate preparation was examined in eight adult males during a 56-d metabolic balance study. The ingestion of the milk or Ca supplements had no overall effect on Ca retention by these subjects because the milk and supplements depressed apparent absorption of Ca in the gut and fractional tubular reabsorption of Ca in the kidneys. Supplementation of the diet with CaCl and to a lesser extent with milk significantly increased renal acid excretion whereas supplementation with CaCO3 depressed renal acid excretion. The three Ca supplements significantly altered magnesium and phosphorus absorption and urinary excretion in different manners but had no overall effect on retention of P or Mg. The responses of our subjects to these treatments may be different than those of subjects who are chronically in negative balance in regard to Ca.     

Properties of the lumen membrane of the cortical thick ascending limb of Henle's loop of rabbit kidney

Previous data suggest the cotransport of Na⁺, Cl^?, and K⁺ across the lumen membrane of the cortical thick ascending limb (cTAL) of rabbit nephron. For this cotransporter to operate K⁺ recycling across the lumen membrane has to be postulated. The present data focus on the conductivity properties of the lumen membrane. Methods for impaling individual cells of in vitro perfused cTAL segments are described. The meanPD across the lumen membrane (PD ₁) is 76 mV (lumen positive). Rapid increase in lumen perfusate K⁺ concentration (3.6→18.6 mmol · l^?1) leads to a depolarization ofPD ₁ by 20 mV. Ba²⁺ (3 mmol · l^?1) added to the lumen perfusate inhibits the K⁺ conductive pathway of the lumen membrane, and consequently increases the voltage divider ratio (current pulse induced voltage deflection across the lumen membrane divided by that across the basolateral membrane) from 2 to 36 as well as transepithelial resistance from 34 to 46 Ω cm². From these changes, and with the use of simultaneous equations of the VDR and of Kirchhoff's law, the resistances of the lumen membrane (88 Ω cm²), of the basolateral membrane (47 Ω cm²), and of the paracellular shunt pathway (47 Ω cm²) can be calculated. Using these estimates of the individual resistances and using the observed change inPD ₁ in the K⁺ concentration step experiments (29±3 mV per decade in K⁺ concentration change) an apparent transference number of the lumen membrane for K⁺ in the order of 0.9–1.0 can be calculated. This indicates that the lumen membrane is essentially K⁺ conductive. This conclusion is strengthened further by the results of another series in which no evidence for a Cl^? conductive pathway in the lumen was obtained. The data of this study can be used to calculate the intracellular K⁺ activity of some 90–100 mmol ·l^?1. For this K⁺ activity the K⁺ diffusion from cell to lumen equals the carrier mediated uptake from lumen to cell. This indicates that an essentially complete recycling of K⁺ across the lumen membrane of the cTAL segment is feasible.     

Zinc supplementation and plasma concentration of vitamin A in preterm infants

To assess the effect of zinc supplementation on plasma retinol levels, 24 preterm infants were randomly assigned to receive 400 micrograms.kg-1.d-1 of intravenous Zn or no Zn supplementation. Intakes of protein, energy, and vitamin A were similar for both groups as were day 0 plasma concentrations of retinol, retinol-binding protein (RBP), and Zn. Zn concentrations were not significantly different between groups at any time during the 3-wk study; however, retinol values in wk 1 increased more in the supplemented group (delta = 10.0 vs 0.9 micrograms/dL, or 0.35 vs 0.031 mumol/L; p less than 0.005). RBP appeared to increase more in the supplemented group but did not reach statistical significance. We hypothesize that the increase in plasma retinol levels noted in the preterm infants receiving Zn supplementation may be mediated by an increased production of RBP in the liver that in turn enhances the hepatic release of retinol.