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A B S T R A C T The purpose of the lpresent studies was to characterize the nature of salt and water transport out of the superficial (SF) and juxtamnedullary (JIM) straight segments of rabbit proximal tubules as examined by in vitro microperfusion techniques. When the perfusate consisted of a solution simulating ultrafiltrate of plasma, there were no differences between SF and J.M straight tubules in either net reabsorption of fluid (SF = 0.47 nl/nmm per min; JAI = 0.56 nl/mm per min) or in transtubular potential difference (PD) (SF -2.1 mV; JM' -1.8 mV). Removal of glucose and alanine fronm the perfusate had no effect on the magnitude of the PD in either straight segment. Ouabain decreased both the net reabsorptive rates and the PD. Isosmolal replacement of NaCl by Na-cvclamate (a presumed imipermeant anion) in the perfusate and the bath caused an increase in luminal negativity in both segments whereas similar substitution of NaCl by choline-Cl (nontransported cation) changed the PD to near zero. These studies, therefore, suggest that sodium is transported out of the proximal straight tubules by an active noncoupled process that generates a PD (electrogenic process).When the perfusate consisted of a solution with a high chloride concentration (resulting from greater HCO3 than C1 reabsorption in the proximal convoluted tubule), different PDs in SF and JAI tubules were generated: SF = + 1.6±0.2 mV; J'M --1.3±0.3 mV. This difference in PD was attributed to relative differences in Na and C1 permeal)ilities in these two seg-

Tolvaptan could possibly improve overall survival in decompensated cirrhosis patients with AUS as long as it was demonstrated to be effective in these patients.

A B S T R A C T Studies utilizing in vitro microperfusion were designed to examine whether urea is actively or passively transported across superficial and juxtamedullary straight segments of rabbit proximal tubules. With perfusate and bath solutions containing 1 nrM urea and electrolytes similar to normal plasma, the efflux (lumento-bath) isotopic permeability (X 10-5 cm s-1) of superficial segments was 1.37±0.16 and of juxtamedullary segments was 2.14+0.20. In the same tubules, the influx (bath-to-lumen) isotopic permeability was 3.70±0.35 in superficial segments and 4.75+0.37 in juxtamedullary segments. Despite net water movement in the opposite direction (0.5 nl mm-' min-1), the influx rate was significantly higher than the efflux rate of urea in both groups. With a low perfusion rate (2 nl/min) and equivalent specific activities of ['4C]urea in bath and perfusate, the collected-to-perfused ratio of ['4C]urea, corrected for volume marker change, was 1.07+0.01 in superficial and 1.09+0.01 in juxtamedullary nephrons, thus indicating net secretion in both segments. In separate studies urea influx was inhibited by hypothermia (decrease from 370 to 280C), by phloretin (0.1 mM in bath), by cyanide (1 nmM), but not by probenecid (0.2 mAM). In each case the inhibition was highly significant and reversible. These data suggest that urea is actively secreted by the straight segments of both the superficial and juxtamedullary proximal tubules. These segments may, therefore, contribute significantly to the high urea concentration found at the bend of Henle's loop by micropuncture.

Background: To address the functional roles of genetic polymorphisms of brain-derived neurotrophic factor (BDNF) in Alzheimer's disease (AD) from a neuropsychological aspect, we used a cross-sectional study design to investigate the association between novel single nucleotide polymorphisms (SNPs) of the BDNF gene (Val66Met (G196A) and C270T) and the Frontal Assessment Battery (FAB) score, which reflects executive function as a non-memory cognitive impairment. Methods: One hundred and sixty-nine outpatients with AD or amnestic mild cognitive impairment (A-MCI) were recruited to the study and divided into three genotypic groups for each representative BDNF functional polymorphism as follows: (i) Val66Met (G196A): G/G (n = 45), G/A (n = 104), and A/A (n = 20); and (ii) C270T: C/C (n = 160), C/T (n = 9), and T/T (n = 0). Then, age, sex ratio, duration of illness (months), education years, Mini-Mental State Examination (MMSE) score, behavioral pathology in Alzheimer disease (Behave-AD) score, Clinical Dementia Rating (CDR) ratio, and total and subtest FAB scores were compared between the genotypic groups for each SNP. Results: Significant differences were found in the total (P < 0.01) and subtest (conflicting instructions and prehension behavior; P < 0.01) FAB scores between the C270T polymorphism groups (C/C and C/T), but not among the G196A polymorphism groups. However, no significant differences in age, sex ratio, duration of illness (months), education years, Behave-AD score, CDR ratio, or MMSE score (reflecting attention and memory function) were found between the individual polymorphism genotypes (G196A and C270T). Conclusion: Of the known BDNF polymorphisms, the C270T SNP may influence executive dysfunction as a non-memory cognitive impairment in Japanese patients with AD.

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