Enterohepatic circulation - Physiological, pharmacokinetic and clinical implications

Enterohepatic recycling occurs by biliary excretion and intestinal reabsorption of a solute, sometimes with hepatic conjugation and intestinal deconjugation. Cycling is often associated with multiple peaks and a longer apparent half-life in a plasma concentration-time profile. Factors affecting biliary excretion include drug characteristics (chemical structure, polarity and molecular size), transport across sinusoidal plasma membrane and canniculae membranes, biotransformation and possible reabsorption from intrahepatic bile ductules. Intestinal reabsorption to complete the enterohepatic cycle may depend on hydrolysis of a drug conjugate by gut bacteria. Bioavailability is also affected by the extent of intestinal absorption, gut-wall P-glycoprotein efflux and gut-wall metabolism. Recently, there has been a considerable increase in our understanding of the role of transporters, of gene expression of intestinal and hepatic enzymes, and of hepatic zonation. Drugs, disease and genetics may result in induced or inhibited activity of transporters and metabolising enzymes. Reduced expression of one transporter, for example hepatic canalicular multidrug resistance-associated protein (MRP) 2, is often associated with enhanced expression of others, for example the usually quiescent basolateral efflux MRP3, to limit hepatic toxicity. In addition, physiologically relevant pharmacokinetic models, which describe enterohepatic recirculation in terms of its determinants (such as sporadic gall bladder emptying), have been developed. In general, enterohepatic recirculation may prolong the pharmacological effect of certain drugs and drug metabolites. Of particular importance is the potential amplifying effect of enterohepatic variability in defining differences in the bioavailability, apparent volume of distribution and clearance of a given compound. Genetic abnormalities, disease states, orally administered adsorbents and certain coadministered drugs all affect enterohepatic recycling.

Physiological responses to the menstrual cycle - Implications for the development of heat illness in female athletes

Fluctuations in estrogen and progesterone during the menstrual cycle can cause changes in body systems other than the reproductive system. For example, progesterone is involved in the regulation of fluid balance in the renal tubules and innervation of the diaphragm via the phrenic nerve. However, few significant changes in the responses of the cardiovascular and respiratory systems, blood lactate, bodyweight, performance and ratings of perceived exertion are evident across the cycle. Nevertheless, substantial evidence exists to suggest that increased progesterone levels during the luteal phase cause increases in both core and skin temperatures and alter the temperature at which sweating begins during exposure to both ambient and hot environments. As heat illness is characterised by a significant increase in body temperature, it is feasible that an additional increase in core temperature during the luteal phase could place females at an increased risk of developing heat illness during this time. In addition, it is often argued that physiological gender differences such as oxygen consumption, percentage body fat and surface area-to-mass ratio place females at a higher risk of heat illness than males. This review examines various physiological responses to heat exposure during the menstrual cycle at rest and during exercise, and considers whether such changes increase the risk of heat illness in female athletes during a particular phase of the menstrual cycle.

High-frequency climatic oscillations recorded in a Holocene coral reef at Leizhou Peninsula, South China sea

A detailed study of the Goniopora reef profile at Dengloujiao, Xuwen County, Leizhou Peninsula, the northern coast of the South China Sea suggests that a series of high-frequency, large-amplitude and abrupt cold events occurred during the Holocene Hypsithermal, an unusual phenomenon termed Leizhou Events in this paper. This period (corresponding to C-14 age of 6.2 -6.7 kaBP or calendar age of 6.7-7.2 kaBP), when the climatic conditions were ideal for coral. reefs to develop, can be divided into at least nine stages. Each stage (or called a climate optimum), lasting about 20 to 50 a, was terminated by an abrupt cold nap and (or) a sea-level lowering event in winter, leading to widespread emergence and death of the Goniopora corals, and growth discontinuities on the coral surface. Such a cyclic process resulted in the creation of a > 4m thick Goniopora reef flat. During this period, the crust subsided periodically but the sea level was rising. The reef profile provides valuable archives for the study of decadal-scale mid-Holocene climatic oscillations in the tropical area of South China. Our results provide new evidence for high-frequency climate instability in the Holocene Hypsithermal, and challenge the traditional understanding of Holocene climate.

On the volume of 4-cycle trades

A 4-cycle trade of volume t corresponds to a simple graph G without isolated vertices, where the edge set can be partitioned into t 4-cycles in at least two different ways such that the two collections of 4-cycles have no 4-cycles in common. The foundation of the trade is v = \V(G)\. This paper determines for which values oft and a there exists a 4-cycle trade of volume t and foundation v.

Life cycle evolution in the Digenea: a new perspective from phylogeny

We use a new molecular phylogeny, developed from small and large subunit ribosomal RNA genes, to explore evolution of the digenean life cycle. Our approach is to map character states on the phylogeny and then use parsimony to infer how the character evolved. We conclude that, plesiomorphically, digenean miracidia hatched from eggs and penetrated gastropod first intermediate hosts externally. Fork-tailed cercariae were produced in rediae and emerged from the snail to be eaten directly by the teleost definitive host. These plesiomorphic characters are seen in extant Bivesiculidae. We infer that external encystment and the use of second intermediate hosts are derived from this behaviour and that second intermediate hosts have been adopted repeatedly. Tetrapod definitive hosts have also been adopted repeatedly. The new phylogeny proposes a basal dichotomy between 'Diplostomida' (Diplostomoidea, Schistosomatoidea and Brachylaimoidea) and 'Plagiorchiida' (all other digeneans). There is no evidence for coevolution between these clades and groups of gastropods. The most primitive life cycles are seen in basal Plagiorchiida. Basal Diplostomida have three-host life cycles and are associated with tetrapods. The blood flukes (Schistosomatoidea) are inferred to have derived their two-host life cycles by abbreviating three-host cycles. Diplostomida have no adult stages in fishes except by life cycle abbreviation. We present and test a radical hypothesis that the blood-fluke cycle is plesiomorphic within the Diplostomida.

Phylogenetic relationships of Hepatozoon (Haemogregarina) boigae Hepatozoon sp. Haemogregarina clelandi and Haemoproteus chelodina from Australian reptiles to other Apicomplexa based on cladistic analyses of ultrastructural and life-cycle characters

The phylogeny of representative haemozoan species of the phylum Apicomplexa was reconstructed by cladistic analyses of ultrastructural and life-cycle characteristics. The analysis incorporated 4 apicomplexans previously not included in phylogenetic reconstructions: Haemogregarina clelandi from the Brisbane River tortoise (Emydura signata), Hepatozoon sp. from the slaty grey snake (Stegonotus cucullatus), Hepatozoon (Haemogregarina) boigae from the brown tree snake (Boiga irregularis), and Haemoproteus chelodina from the saw-shelled tortoise (Elseya latisternum). There was no apparent correlation between parasite phylogeny and that of their vertebrate hosts, but there appeared to be some relationship between parasites and their intermediate hosts, suggestive of parasite/vector co-evolution.

Skolem-type difference sets for cycle systems

Cyclic m-cycle systems of order v are constructed for all m greater than or equal to 3, and all v = 1(mod 2m). This result has been settled previously by several authors. In this paper, we provide a different solution, as a consequence of a more general result, which handles all cases using similar methods and which also allows us to prove necessary and sufficient conditions for the existence of a cyclic m-cycle system of K-v - F for all m greater than or equal to 3, and all v = 2(mod 2m).

Serum inhibin A and B concentrations during the menstrual cycle in mothers of spontaneous dizygotic twins

Dizygotic twinning in humans is influenced by genetic factors suggesting inherited variation affects follicle development and predisposes to double ovulations. In a previous study, we conducted a detailed examination of follicle development and variation in hormone concentrations during the menstrual cycle in mothers of DZ twins (MODZT) compared with an age-matched control group of mothers of singletons. We did not detect differences in FSH concentrations between mothers of twins and mothers of singletons. Serum inhibin concentrations were measured by a radioimmunoassay that did not distinguish between dimeric inhibin A and B forms and free inhibin alpha subunit. We therefore analyzed the samples from this study with specific assays to determine whether concentrations of inhibin A and B were different between MODZT and controls and therefore contribute to the twinning phenotype. There were no significant differences between MONT with single ovulations and control women in inhibin A and B concentrations during the cycle, including the critical period for the selection of the dominant follicle. These data suggest that the genetic cause of twinning is not associated with changes in FSH concentrations or recognised feedback mechanisms regulating FSH release.

Improved nitrogen removal by application of new nitrogen-cycle bacteria

In order to meet increasingly stringent European discharge standards, new applications and control strategies for the sustainable removal of ammonia from wastewater have to beimplemented. In this paper we discuss anitrogen removal system based on the processesof partial nitrification and anoxic ammoniaoxidation (anammox). The anammox process offers great opportunities to remove ammonia in fully autotrophic systems with biomass retention. No organic carbon is needed in such nitrogenremoval system, since ammonia is used a selectron donor for nitrite reduction. The nitrite can be produced from ammonia in oxygen-limited biofilm systems or in continuous processes without biomass retention. For successful implementation of the combined processes, accurate biosensors for measuring ammonia and nitrite concentrations, insight inthe complex microbial communities involved, and new control strategies have to be developed and evaluated.

Spinal stiffness changes throughout the respiratory cycle

Posteroanterior stiffness of the lumbar spine is influenced by factors, including trunk muscle activity and intra-abdominal pressure (IAP). Because these factors vary with breathing, this study investigated whether stiffness is modulated in a cyclical manner with respiration. A further aim was to investigate the relationship between stiffness and IAP or abdominal and paraspinal muscle activity. Stiffness was measured from force-displacement responses of a posteroanterior force applied over the spinous process of L-2 and L-4. Recordings were made of IAP and electromyographic activity from L-4/L-2 erector spinae, abdominal muscles, and chest wall. Stiffness was measured with the lung volume held at the extremes of tidal volume and at greater and lesser volumes. Stiffness at L-4 and L-2 increased above base-level values at functional residual capacity (L-2 14.9 N/mm and L-4 15.3 N/mm) with both inspiratory and expiratory efforts. The increase was related to the respiratory effort and was greatest during maximum expiration (L-2 24.9 N/mm and L-4 23.9 N/mm). The results indicate that changes in trunk muscle activity and IAP with respiratory efforts modulate spinal stiffness. In addition, the diaphragm may augment spinal stiffness via attachment of its crural fibers to the lumbar vertebrae.

Reproducibility of a laboratory-based 40-km cycle time-trial on a stationary wind-trainer in highly trained cyclists

The purpose of the present study was to examine the reproducibility of laboratory-based 40-km cycle time-trial performance on a stationary wind-trainer. Each week, for three consecutive weeks, and on different days, forty-three highly trained male cyclists ((x) over bar +/- SD; age = 25 +/- 6 y; mass = 75 +/- 7 kg; peak oxygen uptake [(V) over dot O-2 peak] = 64.8 +/- 5.2 ml x kg(-1) x min(-1)) performed: 1) a (V) over dot O-2 peak test, and 2) a 40-km time-trial on their own racing bicycle mounted to a stationary wind-trainer (Cateye - Cyclosimulator). Data from all tests were compared using a one-way analysis of variance. Performance on the second and third 40-km time-trials were highly related (r = 0.96; p < 0.001), not significantly different (57:21 +/- 2:57 vs. 57:12 +/- 3:14 min:s), and displayed a low coefficient of variation (CV) = 0.9 +/- 0.7%. Although the first 40-km time-trial (58:43 +/- 3:17min:s) was not significantly different from the second and third tests (p = 0.06), inclusion of the first test in the assessment of reliability increased within-subject CV to 3.0 +/- 2.9%. 40-km time-trial speed (km x h(-1)) was significantly (p < 0.001) related to peak power output (W; r = 0.75), (V) over dot O-2 peak (1 x min(-1); r = 0.53), and the second ventilatory turnpoint (1 x min(-1); r = 0.68) measured during the progressive exercise tests. These data demonstrate that the assessment of 40-km cycle time-trial performance in well-trained endurance cyclists on a stationary wind-trainer is reproducible, provided the athletes perform a familiarization trial.

Optical experiments beyond the quantum limit: Squeezing entanglement and teleportation

Results of experiments recently performed are reported, in which two optical parametric amplifiers were set up to generate two independently quadrature squeezed continuous wave laser beams. The transformation of quadrature squeezed states into polarization squeezed states and into states with spatial quantum correlations is demonstrated. By utilizing two squeezed laser beams, a polarization squeezed state exhibiting three simultaneously squeezed Stokes operator variances was generated. Continuous variable polarization entanglement was generated and the Einstein-Podolsky-Rosen paradox was observed. A pair of Stokes operators satisfied both the inseparability criterion and the conditional variance criterion. Values of 0.49 and 0.77, respectively, were observed, with entanglement requiring values below unity. The inseparability measure of the observed quadrature entanglement was 0.44. This value is sufficient for a demonstration of quantum teleportation, which is the next experimental goal of the authors.

Speleothem U-series dating of semi-synchronous climate oscillations during the last deglaciation

Evidence for nearly synchronous climate oscillations during the last deglaciation has been found throughout the Northern Hemisphere but few records are based on independent time scales of calendar years. We present a rare uranium-series dated oxygen-carbon isotope record for a speleothem from Tangshan Cave, China, which demonstrates that abrupt deglacial climatic oscillations from 16 800 to 10 500 yr BP are semi-synchronous with those found in Greenland ice core records. Relatively rapid shifts in speleothem oxygen isotope ratios demonstrate that the intensity of the East Asian monsoon switched in parallel with the abrupt transitions separating the Bolling-Allerod, Younger Dryas, and pre-Boreal climatic reversals. However, the dated isotopic transitions appear to have lasted longer. Our results demonstrate the dominant role of atmospheric teleconnections in the rapid propagation of deglacial climatic signals on a hemispheric scale, and highlight the importance of U-series dated speleothems in the timing and characterization of abrupt climate change. (C) 2003 Elsevier B.V. All rights reserved.