Systemic aluminum toxicity: effects on bone, hematopoietic tissue, and kidney

Although the full mechanisms are not yet elucidated, research into the mechanism of toxicity of aluminum (Al) on bone formation and remodeling and on hematopoietic tissue is ongoing. In contrast little information exists on the interactive effects of systemic Al and the kidney. In bone, both clinically and experimentally, high doses of Al inhibit remodeling, slowing both osteoblast and osteoclast activities and producing osteomalacia and adynamic bone disease. In contrast, while very low levels of Al are mitogenic in bones of experimental animals, the effect of low levels of Al in humans is unknown. Aluminum has been shown to have its mitogenic action at the osteoblast, but whether the effect on resorption is viz osteoblast-directed changes in osteoclast activity has not yet been determined. Parathyroid hormone (PTH) levels are disrupted by Al in humans and animals. Whether altered PTH levels play a major or even a minor role in Al-dependent osteotoxicity requires clarification. In hematopoietic tissue, Al causes a microcytic anemia, not reversible by iron. Friend leukemia cells treated with Al have been reported to accumulate excess iron, without incorporating it into ferritin or heme. It is not yet known which steps in iron metabolism are disrupted by Al, if they involve a single mechanism of action, or even if this disruption in iron metabolism accounts for the anemia seen in Al toxicosis. In kidney, research is needed to evaluate Al nephrotoxicity; there are almost no studies in this area. Furthermore, research is needed to evaluate mechanisms of renal Al excretion, presently shown by one study to occur at the distal tubule. Such studies might well throw light on whether Al plays a role in aggravating renal insufficiency, or whether the role of the kidney in Al toxicosis is limited to the causative effect of renal compromise on Al accumulation. In summary, while a number of mechanisms have been proposed for the toxic action of Al, no single mechanism emerges to explain these diverse effects of systemic Al. Recommendations for future research are presented and summarized in Table 1.     

ALCHEMIST: A General Purpose Transformation Generator

ALCHEMIST is a general purpose transformation generating environment, which supports specification, generation and execution of data transformations. ALCHEMIST allows an abstract specification of the transformation through a window-based interface and supports the generation and compilation of transformation program code from these specifications. Unlike compiler-compilers, ALCHEMIST is intended to automate building transformations between two complex representation formats and is thus especially suitable for constructing transformations between database tools, CASE tools, graphical editors or text formatters. In this paper we describe the design principles and the structure of ALCHEMIST, and demonstrate its use. We also discuss our experiences with several example transformations and present a real-life case study of using ALCHEMIST for interfacing two software development environments.     

A Low-Power Integrated Circuit for a Wireless 100-Electrode Neural Recording System

Recent work in field of neuroprosthetics has demonstrated that by observing the simultaneous activity of many neurons in specific regions of the brain, it is possible to produce control signals that allow animals or humans to drive cursors or prosthetic limbs directly through thoughts. As neuroprosthetic devices transition from experimental to clinical use, there is a need for fully-implantable amplification and telemetry electronics in close proximity to the recording sites. To address these needs, we developed a prototype integrated circuit for wireless neural recording from a 100-channel microelectrode array. The design of both the system-level architecture and the individual circuits were driven by severe power constraints for small implantable devices; chronically heating tissue by only a few degrees Celsius leads to cell death. Due to the high data rate produced by 100 neural signals, the system must perform data reduction as well. We use a combination of a low-power ADC and an array of "spike detectors" to reduce the transmitted data rate while preserving critical information. The complete system receives power and commands (at 6.5 kb/s) wirelessly over a 2.64-MHz inductive link and transmits neural data back at a data rate of 330 kb/s using a fully-integrated 433-MHz FSK transmitter. The 4.7times5.9 mm² chip was fabricated in a 0.5-mum 3M2P CMOS process and consumes 13.5 mW of power. While cross-chip interference limits performance in single-chip operation, a two-chip system was used to record neural signals from a Utah Electrode Array in cat cortex and transmit the digitized signals wirelessly to a receiver     

Simultaneous measurements of cytosolic and mitochondrial Ca2+ transients in HT29 cells

Loading of HT29 cells with the Ca2+ dye fura-2/AM resulted in an nonhomogeneous intracellular distribution of the dye. Cellular compartments with high fura-2 concentrations were identified by correlation with mitochondrial markers, cellular autofluorescence induced by UV, and dynamic measurement of autofluorescence after inhibition of oxidative phosphorylation. Stimulation with carbachol (10(-4) mol/liter) increased cytosolic, nuclear, and mitochondrial Ca2+ activity ([Ca2+]c, [Ca2+]n, and [Ca2+]m, respectively) measured by UV confocal and conventional imaging. Similar results were obtained with a prototype two-photon microscope (Zeiss, Jena, Germany) allowing for fura-2 excitation. The increase of [Ca2+]m lagged behind that of [Ca2+]c and [Ca2+]n by 10-20 s, and after removing the agonist, [Ca2+]m also decreased with a delay. A strong increase of [Ca2+]m occurred only when a certain threshold of [Ca2+]c (around 1 micromol/liter) was exceeded. In a very similar way, ATP, neurotensin, and thapsigargin increased [Ca2+]c and [Ca2+]m. Carbonyl cyanide p-trifluoromethoxyphenylhyrdrazone reversibly reduced the increase of [Ca2+]m. The source of the mitochondrial Ca2+ increase had intra- and extracellular components, as revealed by experiments in low extracellular Ca2+. We conclude that agonist-induced Ca2+ signals are transduced into mitochondria. 1) Mitochondria could serve as a Ca2+ sink, 2) mitochondria could allow the modulation of [Ca2+]c and [Ca2+]n signals, and 3) [Ca2+]m may serve as a stimulatory metabolic signal when a cell is highly stimulated.     

Specific blockade of slowly activating I(sK) channels by chromanols -- impact on the role of I(sK) channels in epithelia

Chromanols, which were recently shown to inhibit cAMP-mediated Cl- secretion in colon crypts via a blockade of a cAMP-activated K+ conductance, were analyzed for their effects on distinct cloned K+ channels expressed in Xenopus oocytes. The lead chromanol 293B specifically inhibited I(sK) channels with an IC50 of 7 micromol/l without affecting the delayed rectifier Kv1.1 or the inward rectifier Kir2.1. Moreover, several other chromanols displayed the same rank order of potency for I(sK) inhibition as demonstrated in colon crypts. Finally, we tested the effects of the previously described I(sK) blocker azimilide on cAMP mediated Cl- secretion in rat colon crypts. Similar to 293B azimilide inhibited the forskolin induced Cl- secretion. These data suggest that I(sK) protein induced K+ conductances are the targets for the chromanol 293B and its analogues, and azimilide.     

Review on miniaturized paraffin phase change actuators,valves, and pumps

During the last 15 years, miniaturized paraffin actuation has evolved through the need of a simple actuation principle, still able to deliver large strokes and high actuation forces at small scales. This is achieved by the large and rather incompressible volume expansion associated with the solid-to-liquid phase transition of paraffin. The common approach has been to encapsulate the paraffin by a stiff surrounding that directs the volume expansion toward a flexible membrane, which deflects in a directed stroke. However, a number of alternative methods have also been used in the literature. The most common applications to this date have been switches, positioning actuators, and microfluidic valves and pumps. This review will treat the historical background, as well as the fundamentals in paraffin actuation, including material properties of paraffin. Besides reviewing the three major groups of paraffin actuator applications—actuators, valves, and pumps—the modelling done on paraffin actuation will be explored. Furthermore, a section focusing on fabrication of paraffin microactuators is also included. The review ends with conclusions and outlook of the field, identifying unexplored potential of paraffin actuation.     

Mesophilic and Thermophilic Anaerobic Digestion of Model Kitchen Waste with Variation of Fat Content

Anaerobic digestion of model kitchen waste (MKW) produced on basis of real kitchen waste (KW) is studied in batch tests. The impact of fat content of three MKWs (14.7 %, 23 %, and 27.2 % rapeseed oil content) on the biogas production at mesophilic and thermophilic conditions and two loadings is examined. The loading of 5 g_VSL⁻¹ leads to fast degradation under both temperature modes and the volume of biogas produced is only weakly correlated to the oil content. For the loading of 25 g_VSL⁻¹ a strong retardation of biogas production, high concentration of volatile fatty acids and no correlation of oil content is observed.     

Luminal ATP induces K+ secretion via a P2Y2 receptor in rat distal colonic mucosa

Changes in ambient pressure can elicit the vertigo and bodily disequilibrium known clinically as alternobaric vertigo. Our previous studies showed that changes in middle ear pressure altered the activity of the primary vestibular neuron, and the finding suggests that the pressure-induced vestibular response causes alternobaric vertigo. To investigate the roles played by the round window (RW) and the oval window (OW) in the vestibular response induced by pressure, we measured the change in perilymphatic pressure and the firing rates of primary vestibular neurons after the application of positive or negative pressure to the middle ear. We found an increase in the pressure-induced vestibular response in the group with a closed OW, and a decrease in the group with a closed RW. Measurements showed that the amplitude of the change in perilymphatic pressure in the group with a closed OW did not differ from that in the control group, whereas the amplitude of the perilymphatic pressure change in the group with a closed RW was significantly reduced. A discrepancy between the number of neurons responding and the amplitude of the perilymphatic pressure change in the closed OW group suggests that the vestibular response induced by the change in middle ear pressure was not related solely to the magnitude of the pressure change in the inner ear, but also involved the oval and round windows.     

Indications, adverse effects and complications of lithium therapy

The application of lithium preparations in the therapy and prophylaxis of recidivations of affective psychoses has essentially gathered in point in psychiatry during the last years. Apart from the discussion of the indication, the contraindication and efficacy especially concomitant appearances, side effects and dangers as well as their influencibility are demonstrated, the knowledge of which is of importance also for the physician not dealing with psychiatry.