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We evaluated the skeletal muscle loss in hemodialysis ( HD) patients by bioelectrical impedance analysis ( BIA) and handgrip strength test. Thirty-four HD patients and 16 healthy subjects (control group) were measured for skeletal muscle mass normalized as the skeletal muscle mass index ( SMI), calculated as skeletal muscle mass (kg)/height (m)2 using a tetrapolar bioelectrical impedance plethysmograph. Handgrip strength test was also performed using a hand dynamometer in both groups. In HD patients, the associations of SMI and handgrip strength with age, sex, HD conditions, and HD parameters such as body mass index ( BMI), single-pool Kt/V (sp Kt/ V), normalized protein catabolic rate (n PCR), creatinine generation rate ( CGR) and serum albumin level (Alb) were investigated. SMI of HD patients (4.58 ± 0.95 kg/m2) was significantly lower than that of the control group (5.55 ± 0.80 kg/m2, P < 0.01). The handgrip strength of HD patients (19.9 ± 7.74 kg) was also significantly lower than that of the control group (33.0 ± 8.94 kg, P < 0.01). In HD patients, HD duration was associated with both SMI and handgrip strength. Among HD parameters, sp Kt/ V was negatively associated with both SMI and handgrip strength, BMI and Alb were positively associated with SMI, while n PCR and CGR were associated with neither SMI nor handgrip strength. HD duration independently contributed to skeletal muscle loss and the value of sp Kt/ V may be affected by skeletal muscle loss in HD patients. [ABSTRACT FROM AUTHOR]

Aquaporin-11 (AQP11), a new member of the aquaporin family, is localized in the endoplasmic reticulum (ER). Aqp11-/- mice neonatally suffer from polycystic kidneys derived from the proximal tubule. Its onset is proceeded by the vacuolization of ER. However, the mechanism for the formation of vacuoles and cysts remains to be clarified. Here, we show that Aqp11-/- mice and polycystic kidney disease (PKD) animals share a common pathogenic mechanism of cyst formation. We performed microarray analyses and histochemical staining to characterize the effects of the disruption of Aqp11 on kidneys of 1-wk-old mice. Microarray analyses revealed that the significantly changed functional categories in Aqp11-/- mice were similar to those in PKD animals. Histochemical studies showed expression changes of 3 genes, Myc, Egfr, Egf, which are assumed to be involved in the proliferation of cystic cells in PKD. We actually confirmed the activation of cell proliferation in the proximal tubule cells with vacuolized ER. Furthermore, three genes associated with the remodeling of the extracellular matrix, Mmp12, Timp1, Tgfb1, were up-regulated in the fibroblasts. We also demonstrated the activation of apoptosis via the ER-stress pathway in the proximal tubule cells with vacuolized ER. These results provide new insights into the physiological roles of AQP11. [ABSTRACT FROM AUTHOR]

Aberrant HCO3- transport is a hallmark of cystic fibrosis (CE) and is associated with aberrant Cl-dependent HCO3- transport by the cystic fibrosis transmembrane conductance regulator (CFTR). We show here that HCO3- current by CFTR cannot account for CFTR-activated HCO3- transport and that CFTR does not activate AE1-AE4. In contrast, CFTR markedly activates Cl- and OH-/HCO3- transport by members of the SLC26 family DRA, SLC26A6 and pendrin. Most notably, the SLC26s are electrogenic transporters with isoform-specific stoichiometries. DRA activity occurred at a Cl-/HCO3- ratio &ges;2. SLC26A6 activity is voltage regulated and occurred at HCO3-/Cl- &ges;2. The physiological significance of these findings is demonstrated by interaction of CFTR and DRA in the mouse pancreas and an altered activation of DRA by the R117H and GS51D mutants of CFTR. These findings provide a molecular mechanism for epithelial HCO3- transport (one SLC26 transporter-electrogenic transport; two SLC26 transporters with opposite stoichiometry in the same membrane domain-electroneutral transport), the CE-associated aberrant HCO3- transport, and reveal a new function of CFTR with clinical implications for CE and congenital chloride diarrhea. [ABSTRACT FROM AUTHOR]

The class of Ca2+-permeable cation channels is composed of large families with six transmembrane segments including transient receptor potential, vanilloid receptor (VR), polycystin, epithelial calcium channels and melastatin (MLS). However, most of them are functionally silent and unexpressed in mammalian cells. An investigation of associated proteins made us believe that the blockade of calpain opens the silent channels. Using 1 μM of blockers in whole cellular patch pipette fill we measured currents of Chinese hamster ovary cells transfected by VR-like 1 and 2, polycystin-2, or a MLS-like new member (MLS3S). Significant conductance of every clone with a characteristic rectification by blockers was demonstrated. The permeability of Ca2+ to them is similar to that reported. Western blot suggested that blockers did not affect the assembly of the protein but enabled its cleavage. Therefore, investigation of these families with the blockers may boost our knowledge of electrophysiologic function. [Copyright &y& Elsevier]

Most women experience sleep changes across the menstrual cycle. We applied the ultra-short sleep–wake schedule to healthy females to compare their 24-h sleep propensity rhythms in the follicular and luteal phases. The daytime (09.00–16.30 h) subjective sleepiness and the number of slow wave sleep-containing nap trials increased in the luteal phase compared to the follicular phase, but the mean sleep propensity did not change. During the periods of 17.00–00.30 h and 01.00–08.30 h there were no differences between the two phases. These results suggest that increased daytime sleepiness in the luteal phase may be related to brain mechanisms controlling slow wave sleep. [ABSTRACT FROM AUTHOR]

The aim of this study was to clarify effects of hormonal and temperature rhythms on circadian fluctuations of sleep propensity. Ten healthy females underwent 24-h sleep deprivation and entered the circadian sleep propensity assessment setting under the ultra-short sleep–wake schedule. During the experiment, sleep propensity rhythm, rectal temperature, and 24-h serum hormone profiles (melatonin, cortisol and thyroid-stimulating hormone) were investigated. The circadian sleep propensity rhythms had two apparent peaks (afternoon and nocturnal peaks) and a trough (nocturnal sleep gate). The timings of the nocturnal sleep gate and the nocturnal peak were correlated exclusively with temperature and melatonin rhythms (P < 0.05), while that of the afternoon peak was significantly correlated with habitual wake time and melatonin rhythm. These results indicate that the circadian sleep propensity rhythm is influenced not only by the circadian pacemaker, but also by sleep habit. [ABSTRACT FROM AUTHOR]

Examines the effect of circadian rhythm on hormonal secretion of melatonin, cortisol, thyroid stimulating hormone and growth hormone. Collection of blood and urine samples; Measurement of core temperature; Excretion of melatonin during night-time.

Investigates the diurnal fluctuation of human time production in routine conditions. Influence of circadian process on production; Effect of light-dark cycle on time production; Conditions of the isolation facility.

Mice with inactivation of AQP11 die neonatally with uremia due to polycystic kidneys. Before forming cysts, the proximal tubule develops vacuoles (MCB 25: 7770, 2005). Restricting the water influx may ameliorate the vacuolization. As water entry into proximal tubular cells is conducted mainly by AQP1 at the brushborder membrane, we produced AQP1/11 double knockout mice. Mice lacking the genes for both AQP1 and AQP11 still developed vacuolization and polycysts at the proximal tubule at similar progression rate and degree to AQP11 KO mice. We then examined the effect of half expression of AQP11 (hetero AQP11 KO mice) in AQP1 null mice. Urine osmolarity was not affected by half reduction of AQP11 (588 vs. 625 mOsm, cf. wild 3200). The body weights were similarly reduced (36.2 vs. 36.7%, cf. wild 19%) with similar urine (502 vs. 522 mOsm, cf. wild 3750 mOsm) and serum osmolarity (577 vs. 568 mOsm, cf. wild 377 mOsm) after 60 h dehydration. We then challenged these mice with 50% sucrose (50 ml/kg BW) by peritoneal injection. The development of osmotic nephrosis was similar with typical foamy vacuoles in the proximal tubules. In summary, AQP1 null background does not affect AQP11 KO phenotype and half expression of AQP11 does not affect the kidney function of AQP1 null mice, suggesting minimal interactions of these aquaporins in the proximal tubule. [ABSTRACT FROM AUTHOR]

Background Information: AQP3 (aquaporin 3) in the skin is important for skin moisture as demonstrated by the studies of AQP3-null mice, which have accelerated skin drying. Prevention of dry skin is important not only from a cosmetic but also from a clinical point of view. Primary keratinocyte cultures are cumbersome for screening substances that modulate AQP3 expression., Results: A human keratocarcinoma cell line was found to express AQP3 mRNA and protein, which responded to hypertonic stimulation with sorbitol, suggesting that the AQP3 expression is normally regulated in this cell line. This cell line also expressed the type 1 keratinocyte transglutaminase gene. The AQP3 expression was unaffected by all-trans-retinoic acid up to 10(-6) M. Similarly, the retinoic acid did not increase the AQP3 expression up to 1% concentration in rat skin., Conclusion: This cell line is useful for the screening of candidate substances that modulate AQP3 expression.

Human ABCA8, a new member of the ATP binding cassette (ABC) transporter family, transports certain lipophilic drugs, such as digoxin. To investigate the roles of this transporter, we cloned a mouse homologue of ABCA8, from a mouse heart cDNA library, named ABCA8a. The deduced mouse ABCA8a protein is 66% identical with that of human ABCA8 and possesses features common to the ABC superfamily. It was found that ABCA8a was mainly expressed in the liver and heart, similar to human ABCA8. We further evaluated the effect of acute digoxin (a substrate for ABCA8) intoxication on the mRNA expression of ABCA8 using northern blotting with a 3' non-coding region as a probe to avoid cross-hybridization with other ABCA genes. Following acute digoxin infusion, the mRNA expression of ABCA8 was significantly reduced in the liver 12-24 h after injection (14.7% of vehicle treatment), but not in the heart and kidney. Real-time quantitative polymerase chain reaction analysis confirmed the reduction in ABCA8a mRNA. Similar reductions in ABCA5, ABCA7, ABCA8b and ABCA9 mRNA were also observed. A comparable amount of digitoxin did not affect ABCA8a mRNA expression in the liver. The results suggest that ABCA8 may play a role in digoxin metabolism in the liver.

Background Information: AQP10 (aquaporin 10) is a new member of water channels and two different transcripts have been reported. The difference between these transcripts is in the presence or the absence of an insertion of 475 nt, which leads to a translation frame shift resulting in a different termination of amino acid translation and synthesis of a shorter form of AQP10. Thus an AQP10 molecule deduced from the transcript with an insertion has a distinct C-terminus, different from that translated from the transcript without the insertion. In the present study, we investigated the expression and localization of these AQP10 isoforms., Results: Two transcripts were expressed in human duodenum and jejunum. Western-blot analysis using antibodies for these AQP10 isoforms immunoblotted two bands of approx. 35 and 30 kDa respectively. Immunohistochemistry and immunoelectron microscopy demonstrated localization of the AQP10 with an insertion in the capillary endothelium in villi of the small intestine and the isoform without the insertion in the gastro-entero-pancrestic endocrine cells., Conclusion: The different forms of localization of the AQP10 isoforms indicate that they may play different roles in the proximal portion of human small intestine.