Mannitol enhances intracellular calcium diffusion in the rat ileum--a hypothesis

The addition of 92 or 136 mM mannitol to a modified saline solution that contained 1.25 mM Ca2+ led to a mannitol concentration-dependent increase in the amount of calcium absorbed in 1 h from 8 cm long ileal loops prepared from fasted male Sprague-Dawley rats, with body weights of 190 +/- 10 g. It is argued that this mannitol-enhanced movement of calcium out of the loop cannot have utilized the paracellular pathway, inasmuch as the luminal calcium concentration of the mannitol instillate decreased during the experiment, with a negative calcium gradient between luminal and body fluids. Instead it is proposed that uncomplexed mannitol and the uncharged calcium complex of mannitol entered the ileal cells. The uncomplexed intracellular mannitol would bind additional calcium that had crossed the brush border down its gradient. The increase in total intracellular calcium will raise the effective intracellular gradient and thereby amplify intracellular calcium diffusion. This in turn increases calcium absorption.     

Testing of the spectroscopic method for location of water microleakages in ITER at the L-2M stellarator

Results of testing of a possible method for location of water microleakages in the cooling system of the first wall and vacuum chamber of ITER are presented. The method consists in spectroscopic detection of the emission lines of atoms and ions of the Xe additive dissolved in water. These lines are excited when the water with dissolved Xe contacts the plasma. The high electron cyclotron resonance heating (ECRH) power deposited in a relatively small plasma volume in the L-2M stellarator (P = 0.5 MW, V = 0.24 m³, and the specific heating power ??2 MW/m³) makes it possible to achieve plasma parameters close to those in the edge plasma of ITER for different operating modes, including the H-mode with an edge transport barrier. In test experiments, several lines of Xe ions were revealed suitable for detection of xenon in plasma with parameters close to those in the edge plasma of ITER at leakage rates at a level of ??10^?6 Pa m³ s^?1 and spatial resolution of ??0.5 cm.     

Bmp7 functions via a polarity mechanism to promote cloacal septation

Background

During normal development in human and other placental mammals, the embryonic cloacal cavity separates along the axial longitudinal plane to give rise to the urethral system, ventrally, and the rectum, dorsally. Defects in cloacal development are very common and present clinically as a rectourethral fistula in about 1 in 5,000 live human births. Yet, the cellular mechanisms of cloacal septation remain poorly understood.

Methodology/Principal Findings

We previously detected Bone morphogenetic protein 7 (Bmp7) expression in the urorectal mesenchyme (URM), and have shown that loss of Bmp7 function results in the arrest of cloacal septation. Here, we present evidence that cloacal partitioning is driven by Bmp7 signaling in the cloacal endoderm. We performed TUNEL and immunofluorescent analysis on cloacal sections from Bmp7 null and control littermate embryos. We found that loss of Bmp7 results in a dramatic decrease in the endoderm survival and a delay in differentiation. We used immunological methods to show that Bmp7 functions by activating the c-Jun N-terminal kinase (JNK) pathway. We carried out confocal and 3D imaging analysis of mitotic chromosome bundles to show that during normal septation cells in the cloacal endoderm divide predominantly in the apical-basal direction. Loss of Bmp7/JNK signaling results in randomization of mitotic angles in the cloacal endoderm. We also conducted immunohistochemical analysis of human fetal sections to show that BMP/phospho-SMAD and JNK pathways function in the human cloacal region similar as in the mouse.

Conclusion/Significance

Our results strongly indicate that Bmp7/JNK signaling regulates remodeling of the cloacal endoderm resulting in a topological separation of the urinary and digestive systems. Our study points to the importance of Bmp and JNK signaling in cloacal development and rectourethral malformations.     

Cytokines as mediators of neuroimmune interactions

Cytokines regulate numerous physiological and pathological processes in the central nervous system (CNS), i.e. they function both as immune regulators and neuromodulators. Acting upon the CNS via different ways, cytokines, mainly proinflammatory ones IL-1beta and TNF-alpha, can disturb physiological functions of the CNS, cause neurotoxic and neurodegenerative damage and stimulate IL-1beta synthesis in hypothalamus nuclei and posterior pituitary. They can produce stress-like effects upon the CNS and affect the activity of the axis hypothalamus--pituitary--adrenal glands, levels of neuropeptides in hypothalamic regions of brain, synthesis and utilization of central monoamines. These influences can implement the effects of sensitization, which enhances neuroendocrine responses to later stresses. Microglia and astrocytes, secondary messengers and interaction between hypothalamus and anterior pituitary play an important role in range of these processes as well as in the maintenance of Th1/Th2 cytokine balance.     

Inhibition of Ca-induced calcium release from mitochondria by antiischemic phenol-based antioxidants

Effects of different inhibitors of lipid peroxidation (LP), such as sulphur-containing oligoquinone hypoxen, natural flavonoid dihydroquercetin (DHQ), and β-ionol, on Ca²⁺-induced calcium release from rat liver mitochondria (RLM) were investigated during oxidation of various substrates. The hypothesis about interrelation between antioxidant properties and influence of selected substances on spontaneous calcium release from mitochondria was verified. Degree of antioxidant activity of the selected substances was estimated by the inhibition of LP induced by Fe²⁺/ATP complex in phospholipid emulsion or in rat liver mitochondria (RLM). According to the inhibition efficacy the investigated substances were ordered as follows: β-ionol ≫ hypoxen > DHQ. 50% inhibition of oxygen consumption during LP of phospholipid emulsion was reached in presence of 3.2 ± 0.6 μM of β-ionol, 15.0 ± 1.1 μM of hypoxen, or 19.8 ± 1.7 μM of DHQ. Among the investigated antioxidants hypoxen only decreased spontaneous release of calcium from RLM after calcium accumulation by RLM. The impact of the antioxidants onto calcium current depended on the oxidized substrate. Hypoxen effect was most expressed during the oxidation of NAD-dependent substrate. The direct relationship between the antioxidant activity of the selected antioxidants and their influence on calcium transport in RLM was not revealed. The results indicate that the choice of antiischemic preparations should not only rely on their antioxidant activities.     

Trial of a Soviet diagnostic kit for determining class M immunoglobulins to the hepatitis A virus by immunoenzyme analysis (an anti-HAV IgM test system)

The authors have studied the effectiveness of the first Soviet test system for the diagnosis of hepatitis A by means of the enzyme immunoassay (Diagn-A-Hep), developed at the Institute of Poliomyelitis and Viral Encephalitides, Moscow, under the conditions of different epidemic situations. In the process of this trial the high specificity and sensitivity of this test system, established earlier in the certification and commission trials, have been confirmed. Diagn-A-Hep has proved to be highly effective in the diagnosis of acute forms of hepatitis A and permitted its detection in patients during the incubation period, as well as in patients with anicteric and asymptomatic subclinical forms. Besides clinical diagnosis, the kit Diagn-A-Hep may be used in large-scale seroepidemiological surveys of the immune structure of the population, as well as in detection of HAV in different material under test.