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This study investigated the effect of antihypertensive therapy with lisinopril on plasma cholesterol concentration and erythrocyte catalase activity in hypertensive patients. We observed, for the first time, significant inverse correlations between systolic blood pressure (BP) and erythrocyte catalase activity and between diastolic BP and erythrocyte catalase activity. Plasma total and low density lipoprotein (LDL) cholesterol as well as triglyceride levels were similar between baseline and 1-, 3-, and 6-month treatment values in the same patients; however, systolic and diastolic BP levels were expectedly reduced after the therapy. Thus, there was no association between BP and lipid-cholesterol metabolism. These findings confirm antihypertensive effect of lisinopril and suggest that erythrocyte catalase is involved in BP control in hypertension and antihypertensive therapy.

Angiotensin-converting enzyme inhibitors are effective at reducing blood pressure, whereas statins decrease plasma cholesterol, impeding atherosclerosis. The authors hypothesize that these medications may improve blood pressure by modifying the arginase-nitric oxide synthase system of erythrocytes. In this study, the effects of lisinopril alone versus lisinopril + simvastatin on erythrocyte and plasma arginase enzyme and nitric oxide metabolites are compared. Patients with atherosclerosis and hypertension are randomly assigned to receive lisinopril 10 to 20 mg/d or lisinopril 10 to 20 mg/d plus simvastatin 20 mg/d for 24 weeks. Higher arginase activity is observed in erythrocytes from 100% of patients and mainly recovered after 12 and 24 weeks of treatment with lisinopril or lisinopril + simvastatin. Plasma arginase activity is 3 orders of magnitude lower than erythrocyte arginase activity in all participants, suggesting a lack of its clinical significance. Both treatments cause the increase in plasma $$\hbox{ N }{\hbox{ O }}_{2}^{-}$$ , $$\hbox{ N }{\hbox{ O }}_{3}^{-}$$ , and $$\hbox{ N }{\hbox{ O }}_{2}^{-}$$ + $$\hbox{ N }{\hbox{ O }}_{3}^{-}$$ in 100% of patients. Erythrocyte $$\hbox{ N }{\hbox{ O }}_{2}^{-}$$ + $$\hbox{ N }{\hbox{ O }}_{3}^{-}$$ concentration is greatly decreased in hypertensive patients but recovers after monotherapy and combined therapy. The results show for the first time that lisinopril monotherapy and combined lisinopril + simvastatin therapy exhibit pronounced and equipotential normalizing effects on erythrocyte arginase and nitric oxide synthase activities.

Amyloid β-protein (Aβ) is the major amyloid component of toxic amyloid senile plaques inducing slow neuronal degeneration in brains of Alzheimer's patients. It can induce proteolysis of some cytoskeletal proteins in the neuron; however, studies of proteolytic enzyme activity in different brain regions and their subcellular compartmentalization were not carried out. In this work, the effects of chronic intracerebroventricular administration of Aβ(25-35) on proteolytic enzymes in subcellular fractions from rat brain regions were studied. Mitochondrial and cytosolic caspase-9 and caspase-3 activities in neocortex, cerebellum, and hippocampus were shown to be increased during infusion of Aβ(25-35). In Aβ(25-35)-treated rats, cytosolic calcium-dependent thiol proteases calpain-1 and calpain-2 appeared in mitochondria and lysosomes, causing apparent release of lysosomal cathepsins B and D to mitochondria and of β-galactosidase to the cytosol. The increase in all proteolytic activities in brain subcellular fractions under the influence of administered Aβ suggests that these enzymes could be transferred across intracellular membranes and involved in neurodegeneration., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Angiotensin-converting enzyme inhibitors are effective at reducing blood pressure, whereas statins decrease plasma cholesterol impeding atherosclerosis. It is hypothesized that these medications may improve blood pressure and serum cholesterol by modifying the antioxidative status and energy metabolism of erythrocytes. In this study, the effects of 2 treatments are compared: lisinopril alone versus lisinopril + simvastatin, on erythrocyte antioxidant and energy metabolic enzymes. Patients with atherosclerosis and moderate hypertension are randomly assigned to receive lisinopril 10 to 20 mg/d or lisinopril 10 to 20 mg/d plus simvastatin 20 mg/d for 24 weeks. Higher catalase activity and lower glutathione peroxidase activity are observed in 94% to 100% patients from both groups after 12 and 24 weeks of treatment. Superoxide dismutase activity is increased significantly only after 24 weeks. No changes of glutathione reductase, lactate dehydrogenase, and phosphofructokinase activities are found under any conditions indicated. Both treatments decrease systolic and diastolic blood pressure equally. Only lisinopril + simvastatin treatment decreases plasma total cholesterol and low-density lipoprotein cholesterol. The results show for the first time that lisinopril monotherapy and combined lisinopril + simvastatin therapy exhibit specific and pronounced effects on antioxidant and energy metabolic enzyme activities in erythrocytes of hypertensive patients.

Cytosolic enzymes AMP deaminase and adenosine deaminase (ADA) catalyze AMP and adenosine deamination, constitute rate-limiting steps of adenine nucleotide catabolism and play important roles in cellular energy metabolism. In this study, AMP deaminase and ADA activities of rat liver, neocortex, cerebellum, striatum and hippocampus were investigated in acute ammonia intoxication and subacute CCl(4)-induced hepatitis. Activities of both AMP deaminase and ADA in the liver were elevated by 2.4-4.2-fold (p<0.0001) in both models of hepatotoxic injury as compared with controls. In acute hyperammonemia activities of AMP, deaminase and ADA increased by 46-59% (p<0.02) in the neocortex and did not change in the striatum. In the hippocampus of hyperammonemic rats, only AMP deaminase activity was increased by 48% (p=0.0004), and in the cerebellum only ADA activity was increased significantly (by 26%, p<0.05). The adenylate pool size and energy charge were greatly reduced in the neocortex of hyperammonemic rats. Results suggested that two parallel pathways of AMP breakdown, including AMP deaminase and ADA, respectively, are up-regulated under pathological conditions, probably in order to overcome compensatory synthesis of adenylates, to ensure prompt adenylate pool depletion and reduce the adenylate energy charge in liver and selected brain regions., (Copyright 2009 Elsevier B.V. All rights reserved.)

In hyperammonemia, a decrease in brain ATP can be a result of adenine nucleotide catabolism. Xanthine dehydrogenase (XD) and xanthine oxidase (XO) are the end steps in the purine catabolic pathway and directly involved in depletion of the adenylate pool in the cell. Besides, XD can easily be converted to XO to produce reactive oxygen species in the cell. In this study, the effects of acute ammonia intoxication in vivo on brain adenine nucleotide pool and xanthine and hypoxanthine, the end degradation products of adenine nucleotides, during the conversion of XD to XO were studied. Injection of rats with ammonium acetate was shown to lead to the dramatic decrease in the ATP level, adenine nucleotide pool size and adenylate energy charge and to the great increase in hypoxanthine and xanthine 11 min after the lethal dose indicating rapid degradation of adenylates. Conversion of XD to XO in hyperammonemic rat brain was evidenced by elevated XO/XD activity ratio. Injection of MK-801, a NMDA receptor blocker, prevented ammonia-induced catabolism of adenine nucleotides and conversion of XD to XO suggesting that in vivo these processes are mediated by activation of NMDA receptors. The in vitro dose-dependent effects of sodium nitroprusside, a NO donor, on XD and XO activities are indicative of the direct modification of the enzymes by nitric oxide. This is the first report evidencing the increase in brain xanthine and hypoxanthine levels and adenine nucleotide breakdown in acute ammonia intoxication and NMDA receptor-mediated prevention of these alterations.

Acute intoxication with large ammonia doses leads to activation of NMDA receptors in the brain, resulting in oxidative stress and disturbance of mitochondrial function. Altered mitochondrial function is a crucial step in some mechanisms of cellular apoptosis. This study assesses whether ammonia intoxication in vivo leads to induction of apoptotic markers such as permeability transition pore (PTP) formation, caspase-3, and caspase-9 activation, changes in p53 protein, or cytochrome c release. Acute ammonia intoxication did not affect caspase-9 or caspase-3 activities. The mitochondrial membrane potential also remained unaltered in non-synaptic brain mitochondria after injection of ammonia, indicating that ammonia did not induce PTP formation in brain in vivo. The nuclear level of p53 did not change, whereas its cytoplasmic level increased approximately two-fold. In agreement with the theory that translocation of the p53 from cytosol to nuclei is an essential step for induction of apoptosis we did not find apoptotic nuclei in brain of rats injected with ammonia. This supports the idea that ammonia neurotoxicity does not involve apoptosis and points to impaired p53 transfer from cytoplasm to nuclei as a possible preventer of apoptosis. We did not find any release of cytochrome c from mitochondria to cytosol after ammonia injection. Cytochrome c content was significantly reduced (30%) in brain mitochondria from rats injected with ammonia. This decrease may contribute to the reduced state 3 respiration, decreased respiratory control index, and disturbances in the mitochondrial electron transport chain in brain mitochondria from rats injected with ammonia., (Copyright 2007 Wiley-Liss, Inc.)

Acute ammonia toxicity is mediated by excessive activation of NMDA receptors. Activation of NMDA receptors leads to activation of poly(ADP-ribose) polymerase (PARP) which mediates NMDA excitotoxicity. PARP is activated following DNA damage and may lead to cell death via NAD+ and ATP depletion. The aim of the present work was to assess whether acute ammonia intoxication in vivo leads to increased PARP in brain cells nuclei and to altered NAD+ and superoxide metabolism and the contribution of NMDA receptors to these alterations. Acute ammonia intoxication increases PARP content twofold in brain cells nuclei.NAD+ content decreased by 55% in rats injected with ammonia. This was not due to decreased NAD+ synthetase nor increased NAD+ hydrolase activities and would be due to increased NAD+ consumption by PARP. Superoxide radical formation increased by 75% in nuclei of brains of rats injected with ammonia, that also induced protein nitrotyrosylation and DNA damage. Blocking NMDA receptors prevented ammonia-induced PARP, superoxide and nitrotyrosylation increase, DNA damage and NAD+ decrease. These results show that acute ammonia intoxication in vivo leads to activation of NMDA receptors, leading to increased superoxide formation and PARP content and depletion of NAD+ in brain cells nuclei that contribute to ammonia toxicity.

The effects of acute ammonia intoxication on reactive oxygen species production by different sources in rat brain were studied. Ammonia intoxication in vivo leads to reduced activity of superoxide dismutase (SOD), catalase and glutathione peroxidase in brain nonsynaptic mitochondria and increased formation of O(2)(-) by submitochondrial particles. It also results in increased xanthine oxidase (XO) activity and decreased xanthine dehydrogenase (XDH)/XO activity ratio indicating conversion of XDH to XO and also increases monoamine oxidase A (MAO-A) activity but not of MAO-B. Blocking NMDA receptors with MK-801 prevents ammonia-induced oxidative stress, XDH to XO conversion and MAO-A activation. Ammonia intoxication did not lead to H(2)O(2) formation by mitochondria, in spite of increased O(2)(-) generation. The main source of H(2)O(2) in the mitochondrial matrix was Mn-SOD. Ammonia intoxication in vivo leads to increased superoxide and decreased hydrogen peroxide in nonsynaptic brain mitochondria. Increased superoxide is due to increased formation by the respiratory chain and by xanthine and aldehyde oxidases and decreased elimination by antioxidant enzymes. The reduced formation of hydrogen peroxide is due to the reduced activity of Mn-SOD. Prevention of ammonia-induced production of reactive oxygen species by MK-801 supports the idea that it is mediated by activation of NMDA receptors.

There is increasing evidence for a critical role of mitochondria in calcium homeostasis and neuronal death in excitotoxicity. In spite of much work during the last two decades, the kinetic parameters of Ca(2+) transport in brain mitochondria remain controversial. Analysis of the literature data suggests that these contradictions can be due to differences in the methodology used to prepare or to incubate brain mitochondria. In the present communication, the whole protocol for preparation of non-synaptic rat forebrain mitochondria is described. This report shows that this preparation is well coupled and essentially free of non-mitochondrial contaminants. The mitochondria obtained are useful to study Ca(2+) uptake and release. Both Na(+)-independent, Na(+)-dependent and spontaneous Ca(2+) release may be studied with this preparation. This system is also useful in studies on the role of mitochondria and other intracellular Ca(2+) stores in disturbance of Ca(2+) homeostasis and delayed cell death under excitotoxic conditions.

This study describes a task that combines random searching with goal directed navigation. The testing was conducted on a circular elevated open field (80 cm in diameter), with an unmarked target area (20 cm in diameter) in the center of 1 of the 4 quadrants. Whenever the rat entered the target area, the computerized tracking system released a pellet to a random point on the open field. Rats were able to learn the task under light and in total darkness, and on a stable or a rotating arena. Visual information was important in light, but idiothetic information became crucial in darkness. Learning of a new position was quicker under light than in total darkness on a rotating arena. The place preference task should make it possible to study place cells (PCs) when the rats use an allothetic (room frame) or idiothetic (arena frame) representation of space and to compare the behavioral response with the PCs' activity.

Continuous rotation of an arena in a cue-rich room dissociates the stationary room-bound information from the rotating arena-bound information. This disrupted spatial discharge in the majority of place cells from rats trained to collect randomly scattered food. In contrast, most place cell firing patterns recorded from rats trained to solve a navigation task on the rotating arena were preserved during the rotation. Spatial discharge was preserved in both the task-relevant stationary and the task-irrelevant rotating reference frames, but firing was more organized in the task-relevant frame. It is concluded that, (i) the effects of environmental manipulations can be understood with confidence only when the rat's purposeful behavior is used to formulate interpretations of the data, and (ii) hippocampal place cell activity is organized in multiple overlapping spatial reference frames.

Foraging rats learned to avoid footshock that was present in a part of a circular arena that was either stable or rotating slowly in a lighted room. The rotation dissociated spatial information in the separate reference frames of the room and arena. After learning to avoid the shocked region in either condition, in the absence of shock, memory for this place was expressed by simultaneous avoidance of an area defined in the reference frame of the room as well as of an area defined in the reference frame of the rotating arena. Spatial memories in these distinct reference frames were acquired, retrieved, and extinguished autonomously.

Injection of large doses of ammonium salts leads to the rapid death of animals. However, the molecular mechanisms involved in ammonia toxicity remain to be clarified. We reported that injecting ammonium acetate (7 mmol/kg) to rats increases the production of superoxide and reduces the activities of some antioxidant enzymes in rat liver and brain. We proposed that these effects induced by ammonia intoxication would be mediated by formation of nitric oxide. To test this possibility we tested whether injection of nitroarginine, an inhibitor of nitric oxide synthase, prevents the effects of ammonia intoxication on antioxidant enzymes and superoxide formation. Following injection of ammonia, glutathione peroxidase, superoxide dismutase and catalase activities were decreased in liver by 42%, 54% and 44%, respectively. In brain these activities were reduced by 35%, 46% and 65%, respectively. Glutathione reductase remained unchanged. Superoxide production in submitochondrial particles from liver and brain was increased by more than 100% in both tissues. Both reduction of activity of antioxidant enzymes and increased superoxide radical production were prevented by previous injection of 45 mg/kg of nitroarginine, indicating that ammonia induces increased formation of nitric oxide, which in turn reduces the activity of antioxidant enzymes, leading to increased formation of superoxide.

Injection of large doses of ammonium salts lead to the rapid death of animals. However, the molecular mechanisms involved in ammonia toxicity remain to be clarified. We have tested the effect of injecting 7 mmol/kg of ammonium acetate on the production of superoxide and on the activities of some antioxidant enzymes in rat liver, brain, erythrocytes and plasma. Glutathione peroxidase, superoxide dismutase and catalase activities were decreased in liver and brain (both in cytosolic and mitochondrial fractions) and also in blood red cells, while glutathione reductase activity remained unchanged. Superoxide production in submitochondrial particles from liver and brain was increased by more than 100% in both tissues. Both diminished activity of antioxidant enzymes and increased superoxide radical production could lead to oxidative stress and cell damage, which could be involved in the mechanism of acute ammonia toxicity.

Navigation by means of cognitive maps appears to require the hippocampus; hippocampal place cells (PCs) appear to store spatial memories because their discharge is confined to cell-specific places called firing fields (FFs). Experiments with rats manipulated idiothetic and landmark-related information to understand the relationship between PC activity and spatial cognition. Rotating a circular arena in the light caused a discrepancy between these cues. This discrepancy caused most FFs to disappear in both the arena and room reference frames. However, FFs persisted in the rotating arena frame when the discrepancy was reduced by darkness or by a card in the arena. The discrepancy was increased by 'field clamping' the rat in a room-defined FF location by rotations that countered its locomotion. Most FFs dissipated and reappeared an hour or more after the clamp. Place-avoidance experiments showed that navigation uses independent idiothetic and exteroceptive memories. Rats learned to avoid the unmarked footshock region within a circular arena. When acquired on the stable arena in the light, the location of the punishment was learned by using both room and idiothetic cues; extinction in the dark transferred to the following session in the light. If, however, extinction occurred during rotation, only the arena-frame avoidance was extinguished in darkness; the room-defined location was avoided when the lights were turned back on. Idiothetic memory of room-defined avoidance was not formed during rotation in light; regardless of rotation, there was no avoidance when the lights were turned off, but room-frame avoidance reappeared when the lights were turned back on. The place-preference task rewarded visits to an allocentric target location with a randomly dispersed pellet. The resulting behaviour alternated between random pellet searching and target-directed navigation, making it possible to examine PC correlates of these two classes of spatial behaviour. The independence of idiothetic and exteroceptive spatial memories and the disruption of PC firing during rotation suggest that PCs may not be necessary for spatial cognition; this idea can be tested by recordings during the place-avoidance and preference tasks.

The effects of hyperammonemia induced in vivo by injecting rats with ammonium acetate on oxidative phosphorylation, malate-aspartate shuttle, some related enzyme activities and metabolite levels in brain mitochondria were studied ex vivo. Rats were found to be either ammonia-sensitive (showing convulsions) or ammonia-resistant (without convulsions) after intraperitoneal injection of ammonium acetate (7 mmol/kg). Ammonium acetate administration to ammonia-sensitive rats led to inhibition of State 3 rates of brain mitochondria utilizing pyruvate, glutamate, isocitrate, and succinate as substrates and to decreased respiratory control index. In brain mitochondria isolated from ammonia-resistant animals, the ammonia-induced effect on such State 3 rates was not observed. In brain mitochondria from hyperammonemic rats without convulsions, a small increase in the activity of malate dehydrogenase was observed; glutamate dehydrogenase, succinate dehydrogenase, and aspartate aminotransferase were not affected. In brain mitochondria from rats with ammonia-induced convulsions, the activities of malate dehydrogenase and succinate dehydrogenase were reduced significantly. Ammonium acetate injection to rats was associated with a 5-fold increase in the brain mitochondrial ammonium ion content and a decrease (ca. 50%) in brain mitochondrial glutamate and aspartate; brain mitochondrial malate and 2-oxoglutarate levels remained unchanged. The rate of the malate-aspartate shuttle in brain mitochondria of hyperammonemic rats was decreased by 20% as compared to corresponding rate in control rats. We conclude that acute administration of ammonium acetate induces serious disturbances in the electron-transport chain, interferences of the malate-aspartate shuttle, alterations of the levels of shuttle intermediates and inhibition of the activities of malate and succinate dehydrogenases in brain mitochondria.

The assumption that hippocampal place cells (PCs) form the neural substrate of cognitive maps can be experimentally tested by comparing the effect of experimental interventions on PC activity and place navigation. Conditions that interfere with place navigation (darkness, cholinergic blockade) but leave PC activity unaffected obviously disrupt spatial memory at a post-PC level. Situations creating a conflict between egocentric and allocentric orientation (place navigation in the Morris water maze filled with slowly rotating water) slow down spatial learning. PC recording in rats searching food pellets in a rotating arena makes it possible to determine which firing fields are stable relative to the room (allocentrically dependent on sighted extramaze landmarks), to the surface of the arena (dependent on egocentric path integration mechanisms and intra-arena cues), or disappear during rotation. Such comparison is made possible by the computerized tracking system simultaneously displaying a rat's locomotion and the respective firing rate maps both in the room reference and arena reference frames. More severe conflict between allocentric and egocentric inputs is produced in the field clamp situation when the rat searching food in a ring-shaped arena is always returned by rotation of the arena to the same allocentric position. Ten-minute exposure to this condition caused subsequent disintegration or remapping of 70% PCs (n = 100). Simultaneous examination of PC activity and navigation is possible in the place avoidance task. A rat searching food in a stationary or rotating arena learns to avoid an allocentrically or egocentrically defined location where it receives mild electric footshock. In the place preference task the rat releases pellet delivery by entering an unmarked goal area and staying in it for a criterion time. Both tasks allow direct comparison of the spatial reference frames used by the PCs and by the behaving animal.

A PC-based system with TV input for automatic tracking of a single and contrast object in 2D in a homogeneous and stationary environment has been developed and applied to Morris water maze experiments. Further development of the system aimed at broader support of experiments, reduction of requirements on the stationarity and homogeneity of the scene background and on multiple-object tracking is discussed. The computer control of active light markers of the tracked object applicable to multiple-objects tracking in a time-sharing regime is also mentioned in the conclusion. The latter extension of the system can be applied to kinematic studies in biomechanics, sport and rehabilitation medicine.

We have proposed that acute ammonia toxicity is mediated by activation of the N-methyl-D-aspartate type of glutamate receptors. MK-801, a selective antagonist of these receptors, prevents death of animals induced by acute ammonia intoxication as well as ammonia-induced depletion of ATP. It seems therefore that, following activation of the N-methyl-D-aspartate receptors, the subsequent events in ammonia toxicity should be similar to those involved in glutamate neurotoxicity. As it has been shown that inhibitors of nitric oxide synthetase such as nitroarginine prevent glutamate toxicity, we have tested whether nitroarginine prevents ammonia toxicity and ammonia-induced alterations in brain energy and ammonia metabolites. It is shown that nitroarginine prevents partially (approximately 50%), but significantly death of mice induced by acute ammonia intoxication. Nitroarginine also prevents partially ammonia-induced depletion of brain ATP. It also prevents completely the rise in glucose and pyruvate and partially that in lactate. Injection of nitroarginine alone, in the absence of ammonia, induces a remarkable accumulation of glutamine and a decrease in glutamate. The results reported indicate that nitroarginine attenuates acute ammonia toxicity and ammonia-induced alterations in brain energy metabolites. The effects of MK-801 and of nitroarginine are different, suggesting that ammonia can induce nitric oxide synthetase by mechanisms other than activation of N-methyl-D-aspartate receptors.

Injection of large doses of ammonia into rats leads to depletion of brain ATP. However, the molecular mechanism leading to ATP depletion is not clear. The aim of the present work was to assess whether ammonium-induced depletion of ATP is mediated by activation of the NMDA receptor. It is shown that injection of MK-801, an antagonist of the NMDA receptor, prevented ammonia-induced ATP depletion but did not prevent changes in glutamine, glutamate, glycogen, glucose, and ketone bodies. Ammonia injection increased Na+,K(+)-ATPase activity by 76%. This increase was also prevented by previous injection of MK-801. The molecular mechanism leading to activation of the ATPase was further studied. Na+,K(+)-ATPase activity in samples from ammonia-injected rats was normalized by "in vitro" incubation with phorbol 12-myristate 13-acetate, an activator of protein kinase C. The results obtained suggest that ammonia-induced ATP depletion is mediated by activation of the NMDA receptor, which results in decreased protein kinase C-mediated phosphorylation of Na+,K(+)-ATPase and, therefore, increased activity of the ATPase and increased consumption of ATP.

We have tested the effect of ammonium injection on the activity of acetylcholinesterase in rat brain. Fifteen minutes after ip injection of 7 mmol/kg of ammonium acetate, the activity of acetylcholinesterase in brain was reduced significantly. The inhibitory effect varied in a wide range, with a maximum decrease of 60%, and was proportional to the concentration of ammonia reached in the brain. It is also shown that ammonium salts added in vitro to the assay mixture inhibit acetylcholinesterase in brain homogenates competitively. The Ki values for inhibition of the enzyme in vitro were 7.2 and 8.5 mM for ammonium acetate and ammonium chloride, respectively, when acetylcholinesterase was assayed in rat brain homogenates, and 7.6 and 8.3 mM when assayed in mice brain homogenates. These results suggest that at least part of the neurologic effects of ammonia could be mediated by an increase of acetylcholine as a consequence of the inhibition of acetylcholinesterase.

The PC is and will remain a basic instrument in the laboratory arsenal in the next few years. The key role of the IBM PC and its clones prompted us to develop a universal multifunctional I/O board (UNIMUL) for this computer. The board will make it possible to use the IBM PC for a wide range of tasks from a simple interface for laboratory processing of data to complex IBM PC-based instruments, e.g. a stimulator, signal analyzer, chart recorder. The present article summarizes the experience gathered during the design and application of the described I/O board in more than 10 different IBM PC-based laboratory and clinical systems listed in the Appendix. An example of the application of the I/O board is presented in the conclusion of this report together with the discussion of the future role of new Application-Specific Integration Circuits (ASICs) and single chip processors in this domain.