Subcellular distribution of ionic components in gastric mucosa of the guinea pig

Summary The topographical distribution of cations, anions and polyanions in the guinea-pig stomach has been studied by ultrastructural cytochemical methods. After fixation with the pyroantimonate-osmium tetroxide solution, variable-sized precipitates were localized in the basolateral extracellular space bordering parietal cells or chief cells but not in that bordering mucus-secreting cells. The basal lamina of all gastric cells disclosed a continuous layer of heavy antimonate deposits. Parietal cells disclosed uniformly fine deposits also on the apical plasmalemma both at the main lumen and in the intracellular canaliculi, and revealed, as well, coarse precipitates in the mitochondria. Fixation with a silver acetate-osmium tetroxide solution yielded nitric acid-resistant, silver deposits confined to the luminal surface of the apical plasmalemma in the main lumen and intracellular canaliculi, the lateral intercellular space, the outer surface of the basal plasmalemma and the basal lamina of the parietal cell.Staining with dialyzed iron demonstrated a glycocalyx rich in acid mucosubstance on the basolateral plasmalemma but not on the apical plasmalemma of parietal cells. In contrast, acid glycoconjugate was visualized on the apical plasmalemma of isthmus cells, mucous neck cells and the transitional cell between isthmus and mucous neck cells but little or no acidic glycoconjugate was demonstrated on the basolateral plasmalemma of these cells. The entire plasmalemma of gastroendocrine cells, unlike other epithelial cells, stained uniformly for acidic glycoconjugate. The dialyzed iron and high iron diamine methods stained the outer compartment of mitochondria in parietal cells intensely and that in other gastric cells lightly. These reagents stained the basal lamina of all gastric cells as did ruthenium red. The several characteristic cytochemical properties of parietal cells presumably relate to the unique secretory activity of these cells and are consistent with the view of the intracellular canaliculi of the parietal cell as the main route for hydrogen and chloride ion secretion.     

Studies on the mechanism of Salmonella typhimurium enterotoxin-induced diarrhoea

The unidirectional fluxes of Na⁺ and Cl^? were studied in Salmonella typhimurium enterotoxin-treated rats. There was net secretion of Na⁺ and Cl^? in toxin-treated animals, while in control animals there was net absorption of these ions. In the presence of the Ca²⁺-ionophore, there was net secretion of Na²⁺ and Cl^? in the control group, while the ionophore enhanced the secretion of these ions in experimental anaimals. The calcium channel blocker, verapamil, decreased the secretion induced by salmonella toxin, but could not reverse the secretion of absorption. There was no difference in the net absorption of Ca²⁺ in both the control and experimental animals. There was a significant increase in the intracellular free calcium concentrations in enterocytes isolated from toxin-treated rat intestines as compared to that in enterocytes isolated from control animals. In the presence of PMA (phorobol-12-myristated-13-acetate) there was net secretion of Na⁺ and Cl^? in the control group, while in the experimental group there was no change in the fluxes of these ions. The selective, potent inhibitor of protein kinase C, H-7 (1-(5-isoquinolinylsulphonyl)-2-methylpiperazine)_reversed the secretion of Na⁺ and Cl^? in the toxin-treated group to absorption. The addition of indomethacin also inhibited the secretion induced by salmonella toxin, but failed to reverse it to absorption. However, the addition both H-7 and indomethacin to the experimental group had a partial additive effect. These studies demonstrate that the Salmonella enterotoxin-mediated fluid secretion involved protein kinase C and the arachidonic acid metabolites and perhaps does not involve the extracellular calcium pools.     

生理病理状态下线粒体合成ATP动态调控机制

线粒体是细胞的代谢中心之一,不仅产生大量的ATP为细胞提供能量,还参与多种生物分子（例如核酸、氨基酸、胆固醇和脂肪酸）合成及代谢废物的处理。ATP是细胞重要的“能源货币”,是能量载体和信号分子,参与调节细胞的各种生命活动。动物与人在激烈运动时,ATP消耗速率增加数十倍,但细胞内的ATP仍维持在“设定点”水平,不出现降低。因此,传统生理学观点认为,动物细胞内ATP水平保持恒定。但新的研究结果表明,生物细胞内ATP水平存在波动。生理条件下,增加能量物资（糖、脂和氨基酸等）和氧供,促进线粒体ATP合成,可使细胞内ATP水平出现一过性升高。新的研究证明,在肥胖情况下,由于能量物质的过多供应,细胞内ATP水平出现持续性升高,构成代谢紊乱的源头信号。线粒体ATP合成受多种因素影响,如氧化应激、钙超载、缺氧、线粒体膜通透性增加和线粒体DNA突变等。这些因素与疾病条件下细胞内ATP水平持续降低相关,常见的疾病包括阿尔茨海默症、帕金森疾病、精神分裂症、肿瘤、心衰、全身炎症反应综合征等。本综述简要概述线粒体调节细胞内ATP水平的研究进展,重点讨论造成ATP波动的因素、机制及病理生理学意义。     

Redox imbalance

Substantial evidence implies that redox imbalance attributable to an overproduction of reactive oxygen species or reactive nitrogen species that overwhelm the protective defense mechanism of cells contributes to all forms of Parkinsons disease. Factors such as dopamine, neuromelanin, and transition metals may, under certain circumstances, contribute to the formation of oxygen species such as H₂O₂, superoxide radicals, and hydroxyl radicals and react with reactive nitrogen species such as nitric oxide or peroxinitrite. Mitochodrial dysfunction and excitotoxicity may be a cause and a result of oxidative stress. Consequences of this redox imbalance are lipid peroxidation, oxidation of proteins, DNA damage, and interference of reactive oxygen species with signal transduction pathways. These consequences become even more harmful when genetic variations impair the normal degradation of altered proteins. Therefore, therapeutic strategies must aim at reducing free-radical formation and scavenging free-radicals.     

Proteome Imbalance of Mitochondrial Electron Transport Chain in Brown Adipocytes Leads to Metabolic Benefits

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Post-exercise rehydration in man: effects of electrolyte addition to ingested fluids

This study examined the effects on water balance of adding electrolytes to fluids ingested after exercise-induced dehydration. Eight healthy male volunteers were dehydrated by approximately 2% of body mass by intermittent cycle exercise. Over a 30-min period after exercise, subjects ingested one of the four test drinks of a volume equivalent to their body mass loss. Drink A was a 90 mmol·l^–1 glucose solution; drink B contained 60 mmol·l^–1 sodium chloride; drink C contained 25 mmol·l^–1 potassium chloride; drink D contained 90 mmol·l^–1 glucose, 60 mmol·l^–1 sodium chloride and 25 mmol·l^–1 potassium chloride. Treatment order was randomised. Blood and urine samples were obtained at intervals throughout the study; subjects remained fasted throughout. Plasma volume increased to the same extent after the rehydration period on all treatments. Serum electrolyte (Na⁺, K⁺ and Cl^–) concentrations fell initially after rehydration before returning to their pre-exercise levels. Cumulative urine output was greater after ingestion of drink A than after ingestion of any of the other drinks. On the morning following the trial, subjects were in greater net negative fluid balance [mean (SEM);P<0.02] on trial A [745 (130) ml] than on trials B [405 (51) ml], C [467 (87) ml] or D [407 (34) ml]. There were no differences at any time between the three electrolyte-containing solutions in urine output or net fluid balance. One hour after the end of the rehydration period, urine osmolality had fallen, with a significant treatment effect (P=0.016); urine osmolality was lowest after ingestion of drink A. On the morning after the test, subjects were in greater net negative sodium balance (P<0.001) after trials A and C than after trials B and D. Negative potassium balance was greater (P<0.001) after trials A and B than after C and D. Chloride balance was positive after drink D and a smaller negative balance (P<0.001) was observed after drink B than after A and C. These results suggest that although the measured blood parameters were similar for all trials, better whole body water and electrolyte balance resulted from the ingestion of electrolyte-containing drinks. There appeared, however, to be no additive effect of including both sodium and potassium under the conditions of this experiment.     

Water stress preconditioning and cotton root pressure-flux relationships

Summary A model was developed to describe interactive effects of exposure time and treatment on thermostability of excisedIllicium parviflorum Michx. root cell membranes using electrolyte leakage (L_c) procedures. Roots were moved from 25°C to treatment temperatures between 35°C and 60°C for 30 to 300 min. A sigmoidal response described L_c increases with increasing temperature at selected time exposures and the lethal exposure time decreased exponentially as temperature increased. The lethal temperature (52.0±1.1°C) for a 15 min exposure using this technique was comparable to the critical temperature (52.2±1.2°C) when roots were exposed to gradually increasing temperatures (4°C per h). Total protein content of roots began to decrease as temperatures increased from 35 to 40°C and the temperature corresponding to 50% reduction in total proteins was 49.1±2.2°C.     

Freezing of isolated thylakoid membranes in complex media

Chloroplast thylakoid membranes isolated from spinach leaves (Spinacia oleracea L. cv. Monatol) were subjected to a freeze-thaw treatment in a buffered medium containing 70 mM KCl, 30 mM NaNO₃ and 20 mM K₂SO₄ in different combinations. In the presence of the three predominant inorganic electrolytes, inactivation of photophosphorylation was mainly caused by a decrease in the capacity of the photosynthetic electron transport; release of proteins from the membranes was not manifest and light-induced H⁺ gradient and proton permeability were largely unaffected. Omission of nitrate from the medium had little effect. When either sulfate or chloride or both were omitted prior to freezing, inactivation of photophosphorylation was correlated with stimulation of the phosphorylating electron flow, marked increase in H⁺ permeability and loss of the ability of the thylakoids to accumulate protons in the light. In the absence of sulfate, uncoupling was mainly a consequence of the dissociation of chloroplast coupling factor (CF₁). Partial restoration of proton impermeability and pH gradient occurred upon the addition of N,N-dicyclohexylcarbodiimide (DCCD). When sulfate was present but chloride omitted, CF₁ remained attached to the membranes and the addition of DCCD had no effect, indicating that the increase in proton efflux was caused by a different mechanism. It is concluded that sulfate stabilizes the CF₁ and prevents its release from the membranes, but KCl is also necessary for maintaining the low permeability of the membranes to protons. The importance of complex media for investigations on isolated biomembrane systems is stressed.Abbreviations CF₁ chloroplast coupling factor - DCCD N,N-dicyclohexylcarbodiimide - Hepes 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid I=Santarius 1986 b     

The metabolic environment of cancer

The tumor cell has a very distinctive metabolism. It acts as a metabolic trap for host nutrients thus taking vital compounds for the metabolism of the host. Depending on the particular tumor growing pattern, cancer cells use preferentially glucose or amino acids for their energetic or biosynthetic needs. Lipids, fatty acids in particular, can also be taken up by the tumor cell. In addition, it can also release some compounds into the host circulation which are not normally produced by the original cell before neoplastic transformation. Some of these compounds affect the metabolism of the host in an unfavorable way since they can oppose the host's metabolic responses, which sustain homeostasis. The final product is that the metabolic machinery of these cells allows them to grow continuously in an uncontrolled manner. The consequences of tumor invasion on the host's metabolism are varied. They have, however, one thing in common: the reduction of the metabolic efficiency of the host. Muscular protein depletion, increased gluconeogenesis, uncoupling of oxidative phosphorylation constitute the main metabolic responses of the host as a result of tumor invasion. The net result of all these metabolic changes is profound energy imbalance which normally ends with cachexia and, eventually, death.     

Growth and survival of the superorganism: Ant colony macronutrient intake and investment

In this study, we used two common ant species (Lasius niger and Lasius neoniger) to assay how they translate variation in the diet (both in composition and frequency) into growth. We measured colony development for over 8 months and measured several phenotypic traits of the worker caste, and examined whether forager preference corresponded with diet quality. Optimal colony growth was a balance between survival and growth, and each of these was maximized with different nutrient regimes. Interestingly, forager preference was not totally aligned with the diet that maximized colony growth. Our results highlight that: (a) organism and superorganism size are controlled by the same nutrients, and this may reflect a common molecular basis for size across life's organizational levels, (b) there are nutrient trade‐offs that are associated with life‐history trade‐offs, likely leading to selection for a balanced diet, and (c) the connection between the preference of foragers for different nutrients and how nutrient combinations affect colony success and demographics are complex and only beginning to be understood.