Effects of Bed-Rest on Urea and Creatinine: Correlation with Changes in Fat-Free Mass

Background

Bed-rest experiments are designed for investigation on catabolic effects of hypokinetic conditions and/or for microgravity simulation in on-ground aerospace research. Bed-rest effects include a reduction in fat-free mass and muscle mass. Urea and creatinine are catabolites of endogenous protein and of muscular energetic metabolism which are excreted mainly by the kidney. The study investigated on urea, creatinine, and kidney function during bed-rest.

Methods

Twenty healthy young men underwent a 7-day adaptation period (day-6 to day-0) and a 35-day bed-rest experiment (day1 to day35) during normocaloric diet. Urine were collected from day-3 to day0 (baseline) and from day1 to day35. Blood samples and anthropometrical data were collected at day0 (baseline) and bed-rest days 7, 14, 21, 28, and 35.

Results

Bed-rest reduced plasma volume, weight, fat-free mass, and muscle mass (P<0.001). During bed-rest there was a transient increase in plasma and urinary urea, a decrease in plasma creatinine, and no change in urinary creatinine. The overall integral of changes from day0 to day35 was on average +101.7 mg/dL for plasma urea (95%CI = +43.4/+159.9), +82.2 g/24 h for urinary urea (95%CI = +55.8/+108.7), −2.5 mg/dL for plasma creatinine (95%CI = −3.1/−1.9). Bed-rest reduced plasma cistatyn C also, which was used as mass-independent marker of glomerular filtration rate (−13.1%, P<0.05). Correlations with final reduction in fat-free mass and muscle mass were significant for the overall integral of changes in urinary urea from day0 to day35 (R = 0.706, P<0.001) and for early changes in urinary urea and plasma urea from day0 to day7 (R = 0.566, P = 0.009 and R = 0.715, P<0.001, respectively).

Conclusions

Study results shows that urea is a marker of catabolic conditions secondary to hypokinetic conditions.     

Pelagic cephalopods of the central Mediterranean Sea determined by the analysis of the stomach content of large fish predators

The pelagic cephalopod fauna of the central Mediterranean Sea was investigated through stomach content analyses of large fish predators. A total of 124 Xiphias gladius, 22 Thunnus thynnus, 100 Thunnus alalunga, and 25 Tetrapturus belone were analyzed. Overall, 3,096 cephalopods belonging to 23 species and 16 families were identified. The cephalopod fauna in the study area is dominated by Sepiolidae, Ommastrephidae, and Onychoteuthidae. The sepiolid Heteroteuthis dispar was the most abundant species (n?=?1,402) while the ommastrephid Todarodes sagittatus showed the highest biomass. They can be considered key-species in the pelagic food web of the study area. The neutrally buoyant Histioteuthis bonnellii, H. reversa, and Chiroteuthis veranyi seem to characterize the deeper water layers. Given the difficulty in sampling pelagic cephalopods, the presence of cephalopod beaks in the stomach of predators represents a fundamental tool to assess the biodiversity and the ecological importance of these taxa in the marine ecosystem.     

Micro- and nanopatterning by lithographically controlled wetting

This protocol describes how to perform lithographically controlled wetting (LCW). LCW enables large-area patterning of microstructures and nanostructures of soluble materials, either organic or inorganic, including biological compounds in buffer solutions or compounds for cell guidance. LCW exploits the capillary forces of menisci established under the protrusions of a stamp placed in contact with a liquid film. In the space confined by each meniscus, the self-organization of the deposited solute yields highly ordered structures that replicate the motif of the stamp protrusions. The method does not require any particular infrastructure and can be accomplished by using simple tools such as compact discs or microscopy grids. Compared with other printing methods, LCW is universal for soluble materials, as it does not require chemical binding or other specific interactions between the solute and the surface. A process cycle takes from 2 to 36 h to be completed, depending on the choice of materials.     

New fused benzazepine as selective D3 receptor antagonists. Synthesis and biological evaluation. Part one: [h]-fused tricyclic systems

The synthesis and SAR of a new series of potent and selective dopamine D(3) receptor antagonists is reported. The introduction of a tricyclic [h]-fused benzazepine moiety on the recently disclosed scaffold of 1,2,4-triazol-3-yl-thiopropyl-tetrahydrobenzazepines is reported. A full rat pharmacokinetic characterization is also reported.     

Frequency of holoprosencephaly in the International Clearinghouse Birth Defects Surveillance Systems: searching for population variations

BACKGROUND: Holoprosencephaly (HPE) is a developmental field defect of the brain that results in incomplete separation of the cerebral hemispheres that includes less severe phenotypes, such as arhinencephaly and single median maxillary central incisor. Information on the epidemiology of HPE is limited, both because few population‐based studies have been reported, and because small studies must observe a greater number of years in order to accumulate sufficient numbers of births for a reliable estimate. METHODS: We collected data from 2000 through 2004 from 24 of the 46 Birth Defects Registry Members of the International Clearinghouse for Birth Defects Surveillance and Research. This study is based on more than 7 million births in various areas from North and South America, Europe, and Australia. RESULTS: A total of 963 HPE cases were registered, yielding an overall prevalence of 1.31 per 10,000 births. Because the estimate was heterogeneous, possible causes of variations among populations were analyzed: random variation, under‐reporting and over‐reporting bias, variation in proportion of termination of pregnancies among all registered cases and real differences among populations. CONCLUSIONS: The data do not suggest large differences in total prevalence of HPE among the studied populations that would be useful to generate etiological hypotheses. Birth Defects Research (Part A), 2008. © 2008 Wiley‐Liss, Inc.     

One drug for two targets: Biological evaluation of antiretroviral agents endowed with antiproliferative activity

AIDS-related cancer diseases are malignancies with low incidence on healthy people that affect mostly subjects already immunocompromised. The connection between HIV/AIDS and these cancers has not been established yet, but a weakened immune system is certainly the main cause. We envisaged the possibility to screen a small library of compounds synthesized in our laboratory against opportunistic tumors mainly due to HIV infection like Burkitt’s Lymphoma. From cellular assays and gene expression analysis we identified two promising compounds. These derivatives have the dual action required inhibiting HIV replication in human TZM-bl cells infected with HIV-1 NL4.3 and showing cytotoxic activity on human colon HT-29 and breast adenocarcinoma MCF-7 cells. In addition, preclinical in vitro adsorption, distribution, metabolism, and excretion studies highlighted a satisfactory pharmacokinetic profile.     

Phthalazine PDE4 inhibitors. Part 3: the synthesis and in vitro evaluation of derivatives with a hydrogen bond acceptor.

This communication describes the synthesis and in vitro evaluation of a novel and potent series of phthalazine phosphodiesterase type (IV) (PDE4) inhibitors. The interaction with two distinct polar binding sites allowed us to eliminate the cyclopentyloxy substitution from rolipram-like analogues.     

The mutation K30D disrupts the only salt bridge at the subunit interface of the homodimeric hemoglobin from Scapharca inaequivalvis and changes the mechanism of cooperativity.

The subunit interface of the homodimeric hemoglobin from Scapharca inaequivalvis, HbI, is stabilized by a network of interactions that involve several hydrogen-bonded structural water molecules, a hydrophobic patch, and a single, symmetrical salt bridge between residues Lys-30 and Asp-89. Upon mutation of Lys-30 to Asp, the interface is destabilized markedly. Sedimentation equilibrium and velocity experiments allowed the estimate of the dimerization constants for the unliganded (K(1,2D) = 8 x 10(4) M(-1)) and for the CO-bound (K(1,2L) = 1 x 10(3) m(-1)) and oxygenated (K(1,2L) = 70 m(-1)) derivatives. For the oxygenated derivative, the destabilization of the subunit interface with respect to native HbI corresponds to about 8 kcal/mol, an unexpectedly high figure. In the K30D mutant, at variance with the native protein, oxygen affinity and cooperativity are strongly dependent on protein concentration. At low protein concentrations (e.g. 1.2 x 10(-5) m heme), at which the monomeric species becomes significant also in the unliganded derivative, oxygen affinity increases and cooperativity decreases. At protein concentrations where both derivatives are dimeric (e.g. 3.3 x 10(-3) m heme), both cooperativity and oxygen affinity decrease. Taken together, the experimental data indicate that in the K30D mutant, the mechanism of cooperativity is drastically altered and is driven by a ligand-linked monomer-dimer equilibrium rather than being based on a direct heme-heme communication as in native HbI.     

Ecosystem-scale flux of CO2 from a restored vacuum harvested peatland

At the ecosystem scale, the water and gasexchange processes are strongly coupled.Drainage and removal of a peatland'ssurface vegetation cover for peatharvesting alters its hydrology, and as adirect consequence the carbon budget.Previous studies have measuredpeatland-atmosphere carbon exchange usingthe chamber methodology. These studies haveindicated that the spatial and temporalvariability is large, suggesting the needfor continuous ecosystem-scalemeasurements. This paper presents ecosystemscale measurements of the atmosphericexchange of water and carbon dioxide(CO₂) from a restored vacuum-harvestedpeatland in eastern Québec, Canada,using the eddy correlation measurementapproach.Results indicate that the adoptedrestoration practices reduce the loss ofwater from the peat. Evapotranspirationfrom the restored site was 20 and 25% lessthan that from an adjacent abandonedcomparison site in 2000 and 2001respectively. However, CO₂ emissionsremain large during non-snow periods (478and 468 g C m^-2 in 2000 and 2001,respectively). The blockage of drainageditches and the existence of a mulch coverat the site keep the moisture and thermalconditions more or less constant.Consequently, the CO₂ flux, which ispredominantly soil respiration, is stronglycontrolled by peat temperaturefluctuations.