Responsiveness to kainate in young rats after 2-week zinc deprivation

On the basis of the evidence of the enhanced susceptibility to kainate-induced seizures in young rats fed a zinc-deficient diet for 4 weeks, the relationship between zinc release from hippocampal neuron terminals and seizure susceptibility was studied in young rats fed the zinc-deficient diet for 2 weeks. Timm’s stain, with which histochemically reactive zinc in the presynaptic vesicle is detected, was not attenuated in mossy fibers and other areas in the hippocampus after 2-week zinc deprivation, whereas the attenuation was observed after 4-week zinc deprivation. Extracellular zinc concentration was not also decreased after 2-week zinc deprivation, unlike the case after 4-week zinc deprivation. To check the capacity for zinc release from neuron terminals after 2-week zinc deprivation, the hippocampus was excessively stimulated with 100 mM KCl. The increase in extracellular zinc concentration of zinc-deficient group was significantly more than that of control group. These results suggest that zinc release from hippocampal neuron terminals is not affected by 2-week zinc deprivation. On the other hand, the latency in myoclonic jerks of zinc-deficient group was significantly shorter than in the control group after treatment with kainate, while the latency in clonic convulsions was not different between the two groups. Intracellular fura-2 signal, a calcium indicator, was significantly higher in the hippocampal CA3 areas of zinc-deficient group 4 s after delivery of kainate to dentate granule cells. These results suggest that susceptibility to kainate-induced seizures is altered prior to the decrease in extracellular zinc concentration and zinc release from neuron terminals in zinc-deficient young rats. The alteration of calcium signaling seems to be involved in the susceptibility in zinc deficiency.     

Hypo-elastic model for lung parenchyma

A simple, isotropic, elastic constitutive model for the spongy tissue in lung is formulated from the theory of hypo-elasticity. The model is shown to exhibit a pressure dependent behavior that has been interpreted in the literature as indicating extensional anisotropy. In contrast, we show that this behavior arises naturally from an analysis of isotropic hypo-elastic invariants and is a result of non-linearity, not anisotropy. The response of the model is determined analytically for several boundary value problems used for material characterization. These responses give insight into both the material behavior as well as admissible bounds on parameters. The model predictions are compared with published experimental data for dog lung.     

Properties of lung parenchyma in distortion.

This study offers a basis for evaluating and developing models of stress-strain behavior of the lung in distortion. Tensile forces were applied along three axes to cubes of dog lung parenchyma. With axially symmetrical force-loading, expansion was reasonably symmetrical and pressure-volume relationships were reasonably conventional in range, hysteresis, and time-dependent behavior. When the force load was changed on one axis only, that axis appeared more compliant than it did during symmetrical loading and the other axes changed length in the opposite sign. Similar distortion was apparent at the alveolar level. Data for five specimens over a range of applied loads are filed with the National Auxiliary Publications Service; graphical examples are presented herein. Relationship among the compliances for symmetrical and asymmetrical loadings were consistent with elastic theory. We derived the elastic coefficients, bulk and Young's moduli, and Poisson's ratio from the data. Poison's ratio was about 0.30 in air-filled specimens, but was lower (0.16-0.24) and increases with stress in saline-filled specimens.     

Bacterial distribution in lung parenchyma early after pulmonary infection with Pseudomonas aeruginosa

Nosocomial infections often cause lethal pneumogenic sepsis. Information on early bacteria-host interaction in the lung is limited. In the present study, mice were sacrificed 60 min and 4 h after Pseudomonas aeruginosa (PA) infection to investigate lung morphology by using electron microscopy and light microscopy. After 1 h, bacteria were found in the alveoli partly in contact with surfactant. Alveolar macrophages were seen with up to 10 intracellular bacteria close to protrusions of alveolar epithelial type I cells and the gas/blood barrier. A rare but surprising finding was bacteria and even replicating bacteria in alveolar epithelial type II cells (AEII). No bacteria were seen in capillaries. Neither engulfment of bacteria by neutrophils nor structural damage of the pulmonary barrier was visible. After 4 h, many neutrophils were found within the capillaries, but also in the alveolar space. Thus, we hypothesize that, in early stages of infection, the uptake of PA even by single AEII can influence the course of the disease.     

Patterns of food intake and self-selection of macronutrients in rats during short-term deprivation of dietary zinc

Although it has been known for more than 50 years that zinc (Zn) deficiency regularly and consistently causes anorexia in many animal species, the basic mechanism(s) that cause this phenomenon still remain(s) an enigma. The following studies describe feeding behavior in the early stages of zinc deficiency in the rat model. In one experiment, we used computerized feeding monitors that measured the intake of individual rats at 10-min intervals over 24-hr periods. Male rats were acclimated to the cages and fed a Zn-adequate egg-white-based diet, or a similar diet with <1.0 mg Zn/kg. Food intake was monitored for seven, consecutive 24-hr periods. The 24-hr food intake pattern of the Zn-deprived rats did not differ from the controls; they simply ate less food, mainly during the night hours, with no differences between groups during the day. Although Zn-deprived rats ate less food than controls, the percentage of total diet consumed during night and day did not differ between groups. In another experiment, we simultaneously offered male rats three isocaloric diets with different macronutrient compositions and with or without adequate Zn, and measured the amount of each diet selected during seven, 24-hr periods. The three diets contained either 57% protein from egg white, 30% fat from soybean oil, or 80% carbohydrate from a combination of starch, hydrolyzed starch, and sucrose. For the first four days on experiment, rats selected similar amounts of each diet. Then the Zn-deprived rats began to select only 50% as much of the protein diet as the controls. Similar results were obtained when the data were expressed on the basis of each macronutrient as a percentage of the total diet selected. Zn-deprived rats selected a diet that contained 8% protein, 73% carbohydrate, and 6% fat while the Zn-adequate rats selected 12% protein, 69% carbohydrate, and 6% fat. Fat intake was not affected by Zn-deprivation. The results confirm our previous findings, and are discussed in terms of Zn-deprivation blunting the pathways of signal transduction that involve the peptide hormones known to affect food intake regulation.     

Impairment of GABAergic neurotransmitter system in the amygdala of young rats after 4-week zinc deprivation

On the basis of the evidence that the excitability of hippocampal glutamatergic neurotransmitter system is enhanced by dietary zinc deficiency, the response of amygdalar neurotransmitter system was checked in young rats fed a zinc-deficient diet for 4 weeks. Extracellular zinc concentration in the amygdala, which was measured by the in vivo microdialysis, was almost the same as that in the hippocampus and decreased by zinc deficiency. Extracellular zinc concentration in the amygdala was increased both in the control and zinc-deficient rats by stimulation with 100 mM KCl, suggesting that the increase in extracellular zinc in the amygdala, as well as that in the hippocampus, is linked with neuronal depolarization. In amygdalar extracellular fluid, the basal glutamate concentration was not significantly different between the control and zinc-deficient rats and was increased to almost the same extent between them by stimulation with 100 mM KCl, unlike more increase in extracellular glutamate concentration in the hippocampus in zinc deficiency. On the other hand, the basal GABA concentration in the amygdalar extracellular fluid was significantly lower in zinc-deficient rats and was not increased both in the control and zinc-deficient rats by stimulation with 100 mM KCl. These results suggest that GABAergic neurotransmitter system is critically impaired in the amygdala of young rats after 4-week zinc deprivation.     

A strain energy function for lung parenchyma

The strain energy for the air-filled lung is calculated from a model of the parenchymal microstructure. The energy is the sum of the surface energy and the elastic energies of two tissue components. The first of these is the peripheral tissue system that provides the recoil pressure of the saline-filled lung, and the second is the system of line elements that form the free edges of the alveolar walls bordering the alveolar ducts. The computed strain energy is consistent with the observed linear elastic behavior of parenchyma and the data on large deformations around blood vessels.     

Ascorbic acid promotes prostanoid release in human lung parenchyma

Ascorbic acid reduces airway reactivity to inhaled bronchoconstrictor agents in man and guinea pigs. The precise mechanism(s) responsible for this effect are unknown, but in both species an acute indomethacin treatment reverses the action of the ascorbic acid. To determine if ascorbic acid promotes prostanoid synthesis and/or inhibits degradation, human lung parenchymal slices (100-200 mg) were incubated for 60 minutes in oxygenated Tyrode's solution alone or with sodium ascorbate (0.001 M-1 M) and/or methacholine (1 microM-100 microM) and/or indomethacin (0.17 microM-17 microM). Aliquots of the incubation medium were assayed by radioimmunoassay for PGE2, PGF2 alpha, thromboxane B2 and 6-keto-PGF1 alpha. Ascorbic acid increased the accumulation of all four prostanoids in the incubation medium, especially thromboxane B2 and 6-keto-PGF1 alpha. This stimulatory effect of ascorbic acid was concentration-dependent and was inhibited by indomethacin. We conclude that ascorbic acid can alter prostanoid generation by human lung tissue and this effect may, in part, explain its antibronchoconstrictor activity in man.     

Isolation of inclusion bodies from rabbit lung parenchyma

The mitochondrial-plus-lysosomal fraction of rabbit lung parenchyma was studied by equilibrium density centrifugation in continuous sucrose density gradients (specific gravity 1.035 to 1.250). High concentrations of lysosomal marker enzymes were found both in a broad band at density 1.15–1.18, a density typical for lysosomes, and in a band at density 1.06–1.07. This light density band also had the highest specific activity of phospholipid, which thin layer and gas-liquid chromatography showed to be primarily lecithin with a high content of palmitic acid residues. Electron microscopy of material from the light density band showed a homogeneous array of particles which bear a strong resemblance to the inclusion bodies of the type II alveolar epithelial cell as seen in electron micrographs of rabbit lung tissue sections. These data suggest that the light density band is an isolation of intact type II alveolar epithelial cell inclusion bodies, which previous studies have implicated as the storage site of the phospholipid moiety of pulmonary surfactant.     

CO2 relaxes parenchyma in the liquid-filled rat lung.

CO(2) regulation of lung compliance is currently explained by pH- and CO(2)-dependent changes in alveolar surface forces and bronchomotor tone. We hypothesized that in addition to, but independently of, those mechanisms, the parenchyma tissue responds to hypercapnia and hypocapnia by relaxing and contracting, respectively, thereby improving local matching of ventilation (Va) to perfusion (Q). Twenty adult rats were slowly ventilated with modified Krebs solution (rate = 3 min(-1), 37 degrees C, open chest) to produce unperfused living lung preparations free of intra-airway surface forces. The solution was gassed with 21% O(2), balance N(2), and CO(2) varied to produce alveolar hypocapnia (Pco(2) = 26.1 +/- 2.4 mmHg, pH = 7.56 +/- 0.04) or hypercapnia (Pco(2) = 55.0 +/- 2.3 mmHg, pH = 7.23 +/- 0.02). The results show that lung recoil, as indicated from airway pressure measured during a breathhold following a large volume inspiration, is reduced approximately 30% when exposed to hypercapnia vs. hypocapnia (P < 0.0001, paired t-test), but stress relaxation and flow-dependent airway resistance were unaltered. Increasing CO(2) from hypo- to hypercapnic levels caused a substantial, significant decrease in the quasi-static pressure-volume relationship, as measured after inspiration and expiration of several tidal volumes, but hysteresis was unaltered. Furthermore, addition of the glycolytic inhibitor NaF abolished CO(2) effects on lung recoil. The results suggest that lung parenchyma tissue relaxation, arising from active elements in response to increasing alveolar CO(2), is independent of (and apparently in parallel with) passive tissue elements and may actively contribute to Va/Q matching.     

Time course of lung parenchyma remodeling in pulmonary and extrapulmonary acute lung injury.

The aim of this study is to test the hypothesis that the early changes in lung mechanics and the amount of type III collagen fiber do not predict the evolution of lung parenchyma remodeling in pulmonary and extrapulmonary acute lung injury (ALI). For this purpose, we analyzed the time course of lung parenchyma remodeling in murine models of pulmonary and extrapulmonary ALI with similar degrees of mechanical compromise at the early phase of ALI. Lung histology (light and electron microscopy), the amount of elastic and collagen fibers in the alveolar septa, the expression of matrix metalloproteinase-9, and mechanical parameters (lung-resistive and viscoelastic pressures, and static elastance) were analyzed 24 h, 1, 3, and 8 wk after the induction of lung injury. In control (C) pulmonary (p) and extrapulmonary (exp) groups, saline was intratracheally (it; 0.05 ml) instilled and intraperitoneally (ip; 0.5 ml) injected, respectively. In ALIp and ALIexp groups, mice received Escherichia coli lipopolysaccharide (10 microg it and 125 microg ip, respectively). At 24 h, all mechanical and morphometrical parameters, as well as type III collagen fiber content, increased similarly in ALIp and ALIexp groups. In ALIexp, all mechanical and histological data returned to control values at 1 wk. However, in ALIp, static elastance returned to control values at 3 wk, whereas resistive and viscoelastic pressures, as well as type III collagen fibers and elastin, remained elevated until week 8. ALIp showed higher expression of matrix metalloproteinase-9 than ALIexp. In conclusion, insult in pulmonary epithelium yielded fibroelastogenesis, whereas mice with ALI induced by endothelial lesion developed only fibrosis that was repaired early in the course of lung injury. Furthermore, early functional and morphological changes did not predict lung parenchyma remodeling.     

Cytoprotective Channels in Mitochondria

Several ion channels are expressed in the inner and outer membranes of mitochondria, but the exact function of these channels is not completely understood. The opening of certain channels is thought to induce the process of cell death or apoptosis. However, other channels of the inner mitochondrial membrane help protect against ischemic injury and oxidative stress. Mitochondrial ATP-sensitive K⁺ channels (mitoK_ATP) and mitochondrial Ca²⁺-activated K⁺ channels (mitoK_Ca) are the primary protective channels that have been identified. In addition to their thermogenic role, certain isoforms of uncoupling proteins are also shown to have protective roles in certain experimental models. This review attempts to provide an updated overview of the proposed mechanism for the protective function of these membrane proteins. Controversies and unanswered questions regarding these channels will also be discussed.     

Structural changes in liver parenchyma of rats kept on diets with various protein contents

The influence of diets with different protein content on the liver structural organization has been studied. Adaptation processes such as hepatocyte proliferation and an increase in the number of secondary lysosomes with the following atrophy of hepatocytes were observed in rats on low protein diet. High protein diet caused hypertrophy of hepatocytes and hyperplasia of subcellular structures.     

Gamma-glutamyltranspeptidase induction by cortisol in liver parenchyma of unweaned rats

In contrast to many differentiated hepatic functions developing after birth, very little is known about in vivo glucocorticoid influences on postnatal expression of fetal liver enzymes, such as GGT. This study showed that cortisol markedly induces liver GGT activity in unweaned rats, but has no effectafter weaning. Enzyme induction was dose- and time-dependent and occurred in parenchymal cells, progressing with time from zone 1 to zone 2 of the liver acinus. Zone-3 hepatocytes were unresponsive even after a 5-day treatment. Lag-times for GGT induction in zones I and 2 of the liver acinus were 1 to 2 days and 2 to 3 days, respectively. From this, a permissive cell change, determined by the hormone administration itself, seems required for the hepatocyte GGT induction by cortisol in pre-weaning rats.     

Over-expression of Zip-13 mRNA in kidney and lung during dietary zinc deficiency in Wistar rats

Zinc is an essential nutrient for all organisms, which is involved in the function of numerous key enzymes in metabolism. Two gene families have been identified involved in zinc homeostasis. ZnT transporters reduce intracellular zinc while Zip transporters increase intracellular zinc. Previous studies in our laboratory have shown that Zip-1, ZnT-1, Zip-2 and LIV-1 mRNA are associated with zinc level in established human breast cancer in nude mice model. In this study, six zinc transporters: ZnT-1, ZnT-2, ZnT-4, Zip-1, Zip-8 and Zip-13 were chosen. We aim to determine the relation between zinc transporters and zinc level in kidney and lung of Wistar rats. Eighteen Wistar rats were randomly divided into three groups: normal group, zinc-deficiency group and pair-fed group. After 22 days, the rats were killed and organs samples were taken, then zinc transporters mRNA were detected by RT-PCR. Compared with the normal group, Zip-13 shows an up-regulation (P < 0.05) in zinc-deficiency group both in kidney and lung, and Zip-8 was significantly lower (P < 0.05) in zinc-deficiency group in kidney.