Microcirculatory disorders in the early period of autotoxic shock

Microcirculation in the rat mesenterium was studied in the early period of autotoxic shock, using light and electron microscopy. Progressive reduction in the number of functioning capillaries, blood flow slowing in microvessels, and increase in the number of leukocytes that adhere to the luminal surface of the endothelium have been noted. Cases of stasis, sludge syndrome, thrombosis of small venules and disturbances of vascular permeability for protein have been observed. Ultrastructural changes: the formation of transendothelial canals and destructive changes in the basal membrane testify to the disturbance of the barrier function in microvessels. The role of free radicals in the pathogenesis of autotoxic shock is discussed.     

Ultrastructure of cells of proper gastric glands and their stroma in hemorrhagic shock in the rat.

Ultrastructural changes in the cells of the proper gastric glands and their stroma are biphasic in the hemorrhagic shock. First phase: "paralysis" of the capillary vessels with an oedema of their stroma, an intracellular oedema with hydropic degeneration of the parietal cells and a degranulation of the argentaffin and argentaffin-like cells. Second phase: ischemia of the gastric mucosa with ultrastructural features of: a) the increased secretion of the parietal cells, b) the degranulation of the chief gastric cells, c) the increased secretion processes in the mucous neck cells. These findings suggest that at last 2 factors coincide in the pathogenesis of so-called stress gastric ulcerations: biphasic disturbances of blood circulation initially damage the gastric mucosa and are followed the digestive hyperactivity of the gastric juice finally resulting stress ulceration.     

Effect of urethan anesthesia on cigarette smoke-induced airway injury in guinea pigs

The effect of urethan anesthesia on cigarette smoke-induced airway responsiveness and permeability was studied in the guinea pig. Airway responsiveness was determined by measuring changes to airway resistance to graded doses of aerosolized histamine, and mucosal permeability was determined by measuring the appearance of fluorescein isothiocyanate-dextran (FITC-D) in the blood and examining its distribution in lung tissue after it had been delivered to the lung in an aerosol. The results confirm previous studies that smoke exposure increased airway responsiveness and mucosal permeability. They also show that urethan anesthesia administered before smoke exposure prevented the smoke-related changes in airway reactivity and mucosal permeability. In animals that remained conscious during the smoke exposure, there was increased deposition of the dextran in the regions of the bronchioloalveolar junctions with a more rapid uptake of FITC-D into the blood. We postulate that, when urethan anesthesia is administered before smoke exposure, the exudative phase of the inflammatory reaction produced by smoke exposure is suppressed.     

Changes in ultrastructure and the occurrence of permeability transition in mitochondria during rat liver regeneration.

Mitochondrial bioenergetic impairment has been found in the organelles isolated from rat liver during the prereplicative phase of liver regeneration. To gain insight into the mechanism underlying this impairment, we investigated mitochondrial ultrastructure and membrane permeability properties in the course of liver regeneration after partial hepatectomy, with special interest to the role played by Ca2+ in this process. The results show that during the first day after partial hepatectomy, significant changes in the ultrastructure of mitochondria in situ occur. Mitochondrial swelling and release from mitochondria of both glutamate dehydrogenase and aspartate aminotransferase isoenzymes with an increase in the mitochondrial Ca2+ content were also observed. Cyclosporin-A proved to be able to prevent the changes in mitochondrial membrane permeability properties. At 24 h after partial hepatectomy, despite alteration in mitochondrial membrane permeability properties, no release of cytochrome c was found. The ultrastructure of mitochondria, the membrane permeability properties and the Ca2+ content returned to normal values during the replicative phase of liver regeneration. These results suggest that, during the prereplicative phase of liver regeneration, the changes in mitochondrial ultrastructure observed in liver specimens were correlated with Ca2+-induced permeability transition in mitochondria.     

Basophilic line of the articular cartilage in normal and various pathological states

Epiphyses of long tubular bones in the man and animals of various age, as well as experimental material of the adjuvant arthritis, with special reference to the basal part of the articular cartilage have been studied by means of histological, histochemical and histometrical methods. The structural-chemical organization of the basophilic line (tidemark) of the articular cartilage ensures its barrier role and participation in regulating selective permeability. Reconstruction of the tidemark in the process of physiological ageing and in cases of the articular pathology is aimed to preserve its integrity and in this way a complete differentiation of the noncalcified and calcified structures is secured. Disturbance of the basophilic line results in changes of the articular selective permeability, in invasion of vessels and structural elements of the bone marrow, and in development of profound distrophic and destructive changes of the cartilage--in deforming artrosis. Deflations in the structural-chemical organization of the tidemark indicate certain disturbances in the state of the system articular cartilage--subchondral bone. These data can be of prognostic importance.     

Permeability Changes Associated with the Action Potential in Procaine-Treated Crayfish Abdominal Muscle Fibers

Permeability changes associated with prolonged action potentials have been analyzed in procaine-treated crayfish abdominal muscle fibers. The effect of external Ca indicates that the increase in membrane conductance observed during the rising phase of the action potential is primarily due to a permeability increase for Ca. A remnant of the permeability increase may cause the succeeding plateau as shown by its high conductance and by the effect of low Mn. A delayed increase in conductance precedes the termination of the plateau phase. This is due to a delayed increase in permeability, probably for K, that is observed when depolarizing electrogenesis is eliminated. High external Ca reduces the action potential duration, the falling phase starting at a higher depolarization. These changes may be related to an earlier onset of the delayed increase in permeability, induced by a larger inside positivity in the presence of higher Ca. No "anomalous rectification" is seen in early or late I-V curves for small depolarizations. Ba may replace Ca in its role in depolarizing electrogenesis, and the first action potential induced in Ba saline has a large overshoot and a long duration. In higher Ba salines, action potentials are greatly prolonged. Long term soaking in Rb-containing or K-free saline also augments and prolongs the action potential. These changes are assumed to be related to depression of the K permeability of the membrane.     

脂质体通透性与脂多型性关系的研究

本文以TPE和TPE/DOPE(1:1.mol:mol)制成包裹荧光分子calcein的脂质体,通过测量荧光强度随扫描温度的变化,探讨了脂质体通透性与脂多型性之间的关系.结果表明,在不发生双层相(L)变成六角形Ⅱ相(H)相转变时,脂质体悬液的荧光强度不增加;当发生该转变时,脂质体悬液的荧光强度开始增加;完成该相转变后,脂质体悬液的荧光强度仍继续增加.据此,我们认为:脂质体的通透性与脂的多型性密切相关,当发生L→HⅡ相转变时,脂质体的通透性增加.由于荧光强度的变化对相变非常敏感,我们建议用测量脂质体荧光强度随温度的变化来监测脂质体稀悬液中脂的多型性.     

Back Diffusion of Hydrogen Ions across Gastric Mucosa of Patients with Gastric Ulcer and Rheumatoid Arthritis

Ionic permeability of the gastric mucosa was measured in six patients with an acute exacerbation of severe generalized rheumatoid arthritis receiving either aspirin and prednisone or aspirin and indomethacin as therapy. The results were compared with those in four patients with benign gastric ulcer and nine normal subjects. Compared with controls H⁺ concentration was decreased and Na⁺ concentration increased while corrected H⁺ flux out of the lumen and Na⁺ flux into the lumen were significantly increased in the patient groups, indicating increased mucosal permeability. Abnormality of the gastric mucosal barrier persisted in two patients despite healing of their ulcers. Mucosal permeability of patients with rheumatoid arthritis and gastric ulcer did not differ significantly from one another. One rheumatoid patient with a gastric ulcer showed no difference in mucosal permeability to that of the other rheumatoid patients. These studies suggest that increased H⁺ ion loss contributes to the apparent hyposecretion of acid in patients gastric ulcer; persistence of an abnormal gastric mucosal barrier to H⁺ ions may explain the high recurrence rate of gastric ulcers; and an abnormal gastric mucosal barrier may be a precursor to gastric ulceration in rheumatoid arthritis.     

Electron microscopy of histamine-induced contraction of the in vitro swine coronary artery.

Dose-dependent contractions of the in vitro swine coronary artery were induced by application of histamine and acetylcholine, but not of angiotensin II, ergonovine, noradrenaline, prostaglandin F2 alpha and serotonin. Ultrastructural changes especially of the tunica intima during the contractions were observed at 2, 5 and 30 min after application of histamine and acetylcholine. The intimal gutter spirally running along the longitudinal axis of the vessel was obscured, and the intimal surface became extensively indented. Exclusively in the histamine-treated samples, the increase in number and size of the intracellular vacuoles and the dilation of the intercellular clefts to the extent of the intercellular vacuoles were observed in the endothelium. Moreover, the enhancement of the endothelial permeability was indicated by the marker experiments using horseradish peroxidase. Such endothelial cell damages and the enhancement of the endothelial permeability may amplify the coronary artery contraction.     

Phase changes in the permeability of the mouse blood-brain barrier after uneven gamma-irradiation

Two phases of changes in blood-brain-barrier permeability for sour fuchsin have been observed in the early period after head or body irradiation at 2.58 C/kg: an increase (up to 2 h) and a decrease (from 2 to 6 h). The correlation between the decrease in BBB permeability and the frequency of clinical manifestations of radiation disease has been established. BBB permeability progressively increased later after head irradiation (24-120 h) which was indicative of its absolute dysfunction. The changes observed may reflect redistribution of fluid and electrolytes in the vascular bed and tissues leading to the onset of brain tissue edema.     

Freezing-induced cellular and membrane dehydration in the presence of cryoprotective agents

Abstract

FTIR and cryomicroscopy have been used to study mouse embryonic fibroblast cells (3T3) during freezing in the absence and presence of DMSO and glycerol. The results show that cell volume changes as observed by cryomicroscopy typically end at temperatures above ?15°C, whereas membrane phase changes may continue until temperatures as low as ?30°C. This implies that cellular dehydration precedes dehydration of the bound water surrounding the phospholipid head groups. Both DMSO and glycerol increase the membrane hydraulic permeability at subzero temperature and reduce the activation energy for water transport. Cryoprotective agents facilitate dehydration to continue at low subzero temperatures thereby decreasing the incidence of intracellular ice formation. The increased subzero membrane hydraulic permeability likely plays an important role in the cryoprotective action of DMSO and glycerol. In the presence of DMSO water permeability was found to be greater compared to that in the presence of glycerol. Two temperature regimes were identified in an Arrhenius plot of the membrane hydraulic permeability. The activation energy for water transport at temperature ranging from 0 to ?10°C was found to be greater than that below ?10°C. The non-linear Arrhenius behavior of Lp has been implemented in the water transport model to simulate cell volume changes during freezing. At a cooling rate of 1°C min^-1, ～5% of the initial osmotically active water volume is trapped inside the cells at ?30°C.     

Structural and functional characteristics of the cellular reaction of the bladder epithelium in the frog to calcium extraction from the apical and basolateral membranes

Extraction of Ca++ ions from cells of the frog urinary bladder serosa side is followed by an increase in the bladder wall permeability for water and inulin. Ultrastructural changes were observed, such as destruction of cell junctions, swelling of the cell and their organelles, reconstruction of the cytoskeleton elements. The free calcium Ringer solution injected in the bladder lumen does not change the permeability of the wall for water and sodium ions. In this case the cell response to the antidiuretic hormone decreases; the ultrastructure of cells and intercellular junctions is not disturbed; the distribution of intramembrane particles on the P- and E-faces of the apical membrane is normal. The above results indicate that there are qualitative differences in the cell response towards the extraction of Ca++-ions between the serosal and mucosal membranes. This also suggests that on the external surface of the apical membrane Ca++ ions may play a very important role in redistribution of intramembrane particles under the action of the antidiuretic hormone.     

“Capillary Permeability” in Patients with Collagen Vascular Diseases

“Capillary permeability” to serum albumin has been measured in patients with collagen vascular diseases by a method which compares the dilution of intravenously injected ¹³¹I-human serum albumin and ⁵¹Cr-R.B.C.s. The results indicate an increased capillary permeability comparable to that which occurs in patients with extensive inflammatory skin disease. We suggest that this increased capillary permeability may be the cause of the episodes of oedema which occur in patients with collagen vascular diseases such as disseminated lupus erythematosus, systemic sclerosis, dermatomyositis, polyarteritis nodosa, and rheumatoid arthritis. “Spontaneous periodic oedema” may be the presenting feature of collagen vascular disease and is due to increased capillary permeability.     

Ultrastructural changes in <Emphasis Type="Italic">Yarrowia lipolytica</Emphasis> cells under stress conditions

Ultrastructural organization of the aerobic yeast Yarrowia lipolytica was studied under conditions of oxidative, heat, and ethanol stresses. It was shown that the following uniform changes in cell ultrastructure did not depend on the type of stress: enlargement of mitochondria, enhanced number and enlargement of peroxisomes, and formation of lipid granules. Similar ultrastructural changes also occurred during the transition of cells to the stationary growth phase. It was shown for the first time that accumulation of polyphosphate granules occurred as a stress response in yeasts. Moreover, numerous globular structures of unknown nature appeared on the cell wall surface under oxidative or heat stress. Under ethanol stress, the cells developed clearly marked deep invaginations of the cytoplasmic membrane. (The same changes in the cytoplasmic membrane were observed in the cells grown on ethanol.) Variations of the cell envelope structure along with the formation of polyphosphate granules were not observed in the stationary growth phase. Ultrastructural changes in the cells under stress conditions are in agreement with the previous data on survival, respiratory activity, and variations of the antioxidant systems.     

Enhanced permeability to sugar associated with muscle contraction. Studies of the role of Ca++

When contractures were induced in isolated frog sartorius muscles with 4 mM caffeine, there was an increase in permeability of the muscle cells to 3-methylglucose. This observation suggests that the changes in permeability to sugar that are known to occur in electrically stimulated muscles may not be intimately related to the depolarization phase of the tissue response. Contractures that were elicited by exposing the muscles to a high concentration of K+ were also associated with an increased permeability to sugar. As the concentration of 45Ca in the medium was raised, more 45Ca entered the muscles during potassium contractures, and the contractures lasted longer, in agreement with the observations of other investigators. There was also a greater change in permeability to sugar when potassium contractures were elicited in the presence of higher concentrations of Ca++. The possibility that the enhanced permeability to sugar may be related to changes in the intracellular concentration of Ca++ is discussed.     

Lysolipid incorporation in dipalmitoylphosphatidylcholine bilayer membranes enhances the ion permeability and drug release rates at the membrane phase transition

The enhanced permeability of lipid bilayer membranes at their gel-to-liquid phase transition has been explained using a "bilayer lipid heterogeneity" model, postulating leaky interfacial regions between still solid and melting liquid phases. The addition of lysolipid to dipalmitoylphosphatidylcholine bilayers dramatically enhances the amount of, and speed at which, encapsulated markers or drugs are released at this, already leaky, phase transition through these interfacial regions. To characterize and attempt to determine the mechanism behind lysolipid-generated permeability enhancement, dithionite permeability and doxorubicin release were measured for lysolipid and non-lysolipid, containing membranes. Rapid release of contents from lysolipid-containing membranes appears to occur through lysolipid-stabilized pores rather than a simple enhancement due to increased drug solubility in the bilayer. A dramatic enhancement in the permeability rate constant begins about two degrees below the calorimetric peak of the thermal transition, and extends several degrees past it. The maximum permeability rate constant coincides exactly with this calorimetric peak. Although some lysolipid desorption from liquid state membranes cannot be dismissed, dialyzation above T(m) and mass spectrometry analysis indicate lysolipid must, and can, remain in the membrane for the permeability enhancement, presumably as lysolipid stabilized pores in the grain boundary regions of the partially melted solid phase.     

Increased permeability of gut mucosa in rats infected with Nippostrongylus brasiliensis.

The permeability of the gut mucosa to macromolecules has been examined in 4 different strains of rats infected with Nippostrongylus brasiliensis (N. brasiliensis). There is a marked increase in mucosal permeability during the infection. In addition, a considerable strain difference is observed in both worm burden kinetics and the kinetics of intestinal permeability. The dose-response and drug treatment experiments in outbred Wistar rats suggest that increased mueosal permeability is a function of the worm burden. However, the increased permeability is related neither to the rapid phase of worm expulsion nor to the rise in intestinal mast cell numbers.     

Electron microscopic studies on the small intestinal mucosa of rats after mechanical intestinal obstruction and ischemia

Ultrastructural changes in the small intestine during the early phase following mechanical obstruction were compared with those after vascular ligation. In both experiments (the early phase of mechanical ileus and ischemia) intestinal epithelial cells at the tips of villi showed common features. One of the most significant changes was an alteration in microvilli, with fragmentation into vesicles, narrowing of apical microvilli and decrease in number. The other change was fatty degeneration of the epithelial cells, which was accompanied by vesiculation of smooth endoplasmic reticulum beneath the terminal webs, fat deposition and dilated Golgi complex containing fat. These observations suggest that in the early phase of mechanical ileus, ischemic damage plays an important role.     

The effect of synthetic polymers on the electrical and permeability properties of lipid membranes

1. The effect of two series of hydrophilic and hydrophobic polymers on the stability, conductivity and permeability towards water and leucine of black lipid membranes and liposomes is reported. 2. The changes in properties of these membrane preparations is related to bulk phase viscosity and dielectric measurements together with monolayer studies. 3. The hydrophobic polymers dramatically increase membrane stability, had no effect on conductivity, but increased the permeability coefficient of leucine. 4. The hydrophilic polymers produced minor, but significant changes to membrane properties. 5. It is concluded that not only basic polymers but also neutral and acidic macromolecules can interact strongly with lipid membranes.     

Ultrastructural changes in the posterior lobe of the pituitary in tetanus poisoning

Ultrastructural studies (electron microscopy) of the caudal part of the hypothalamo-hypophysial neurosecretory system were conducted in rats during experimental tetanus. Its activation was found to occur as soon as the initial period after the injection of the toxin, this being apparently connected with the administration of the heterogenous protein, because inactivated toxin proved to induce the same effect. Changes in the vascular permeability, lipid metabolism and the blood coagulation system were also observed.