Cellular Reserve Research Articles

Microgravity effects and aging physiology: similar changes or common mechanisms?

Despite the use of preventive measures (including intense physical activity), cosmonauts and astronauts develop muscle atony and atrophy, insufficiency of the cardiovascular system, osteopenia, etc. All these changes, reminiscent of age-related physiological changes, occur in a healthy person in microgravity quite quickly - within a few months. Adaptation to the absence of gravity leads to the symptoms of aging, which are compensated after returning to Earth. The prospect of interplanetary flights raises the question of gravity thresholds, below which the main physiological systems will lose their functional potential, similar to aging, and affect life expectancy. An important role in the aging process belongs to the body’s cellular reserve - progenitor cells, which are involved in physiological remodeling and regenerative/reparative processes of all physiological systems. With age, progenitor cell count and the regenerative potential decreases. Moreover, their paracrine spectrum becomes pro-inflammatory during replicative senescence, disrupting tissue homeostasis. Mesenchymal stem/stromal cells (MSCs) are mechanosensitive, and therefore the absence of a gravitational stimulus causes serious changes in their functional status. The review compares the cellular effects of microgravity and changes developing in senescent cells, including stromal precursors.

Inherited Eye Diseases with Retinal Manifestations through the Eyes of Homeobox Genes.

Retinal development is under the coordinated control of overlapping networks of signaling pathways and transcription factors. The paper was conceived as a review of the data and ideas that have been formed to date on homeobox genes mutations that lead to the disruption of eye organogenesis and result in inherited eye/retinal diseases. Many of these diseases are part of the same clinical spectrum and have high genetic heterogeneity with already identified associated genes. We summarize the known key regulators of eye development, with a focus on the homeobox genes associated with monogenic eye diseases showing retinal manifestations. Recent advances in the field of genetics and high-throughput next-generation sequencing technologies, including single-cell transcriptome analysis have allowed for deepening of knowledge of the genetic basis of inherited retinal diseases (IRDs), as well as improve their diagnostics. We highlight some promising avenues of research involving molecular-genetic and cell-technology approaches that can be effective for IRDs therapy. The most promising neuroprotective strategies are aimed at mobilizing the endogenous cellular reserve of the retina.

Asymmetrical endothelial cell migration from invitro Quarter-Descemet membrane endothelial keratoplasty grafts.

PurposeTo investigate in vitro central and peripheral corneal endothelial cell (EC) migration from Quarter–Descemet membrane endothelial keratoplasty (Quarter‐DMEK) grafts.MethodsQuarter‐DMEK grafts were obtained from 10 corneas ineligible for transplantation but with intact and viable ECs. Ten Quarter‐DMEK grafts were ‘sandwiched’ between two glass slides and cultured over 1 week in a humidified atmosphere at 37 °C and 5% CO2. Cell migration was evaluated by light microscopy at standardized time intervals. In addition, immunohistochemistry analyses were performed to assess the detailed structural organization of ECs in the corneal centre and far periphery.ResultsEndothelial cell (EC) migration occurred from the radial cut graft edges, but not from the far peripheral area. Cell migration followed three different migration patterns: (1) individual cell migration, (2) uncoordinated cell migration of cell clusters and (3) collective migration in which ECs moved as a sheet. Immunostaining showed the presence of ECs up to the far periphery but with different expression patterns of phenotypical markers ZO‐1, Na+/K+ ‐ATPase and vimentin compared to central ECs.Conclusion In vitro EC migration from Quarter‐DMEK grafts occurs along the radial cut edges with a decrease in migration activity towards the corneal far periphery. No migration occurred along the outer peripheral corneal edge possibly due to a different anatomical matrix in the far periphery. Hence, ECs from the far periphery may not contribute to corneal clearance of the adjacent bare area after Quarter‐DMEK surgery, but these cells may constitute a valuable cellular reserve on the graft.

Physiological role of Kvβ2 (AKR6) in murine skeletal muscle growth and regulation.

Potassium channel accessory subunits (Kvβ) play a key role in cardiac electrical activity through ion channel modulation. In this study, we hypothesize that Kvβ2 regulates skeletal muscle growth and fibre phenotype via protein-protein interactions. Kvβ2 knockout mouse model was used for morphometric, immunohistochemical and biochemical analysis to evaluate the role of Kvβ2 in skeletal muscle physiology. Deletion of Kvβ2 gene in mice (Kvβ2 knockout, KO) leads to significant decrease in body weight along with skeletal muscle size. Key hindlimb muscles such as biceps, soleus and gastrocnemius were significantly smaller in size in KO mice compared to that of wild type. Morphometric measurements and histological analysis clearly point that the fibre size is decreased in each of the muscle type in KO compared with wild-type mice. In addition, Kvβ2 deletion contributes to fibre-type switching from fast to slow fibre as indicated by more abundant MHCI-expressing fibres in gastrocnemius and soleus muscles, which may underscore the smaller muscle size alongside increase in U3 ubiquitin ligase; NEDD4 expression. Using targeted siRNA knockdown approach, we identified that Kvβ2 knockdown does not affect the myoblasts proliferation. However, Pax7 expression was significantly decreased in 4-week-old gastrocnemius muscle, suggesting that cellular reserve for growth may be deficient in KO mice. This is further supported by decreased migratory capacity of C2C12 cells upon siRNA-targeted Kvβ2 knockdown. Overall, this is the first report identifying that genetic deletion of Kvβ2 leads to decreased skeletal muscle size along with isotype switching.

Melatonin Improves Mitochondrial Respiration in Syncytiotrophoblasts From Placentas of Obese Women.

Maternal obesity is associated with increased oxidative stress but decreased placental mitochondrial respiration and expression of mitochondrial electron transport chain (ETC) complexes I to V. Melatonin acts as an antioxidant and prevents oxidative stress-induced changes in cytotrophoblasts. Placentas were collected at term by cesarean delivery from obese (first trimester body mass index [BMI] ≥30, n = 10) or lean (BMI < 25, n = 6) women. Cytotrophoblasts were isolated and allowed to syncytialize for 72 hours with or without melatonin (0.1-100 µM) for the last 24 hours. Mitochondrial respiratory parameters were measured in a Seahorse XF24. Expression of ETC complexes I to V and antioxidant enzymes was measured by Western blot. Maternal clinical characteristics of patients were similar except for BMI. No significant improvement in mitochondrial respiration occurred with addition of melatonin to trophoblasts of lean women. However, in trophoblasts from obese women, melatonin (10 and 100 µmol/L) significantly increased maximal respiration ( P = .01 and P = .009, respectively) and spare capacity ( P = .02 and P = .003, respectively) compared to the untreated control. No differences were detected in the expression of ETC complexes and superoxide dismutase 1 or 2 in trophoblasts treated with melatonin. The expression of glutathione peroxidase, which was significantly greater in trophoblast of obese compared to lean women ( P < .05), was decreased back to the level seen in trophoblast of lean women with addition of melatonin ( P = .02). Improved spare respiratory capacity, the cellular reserve, could impart a protective effect to the placenta and fetus in an adverse intrauterine environment or in response to additional stressors.

Multipotent stromal cells/mesenchymal stem cells and fibroblasts combine to minimize skin hypertrophic scarring

BackgroundTransplantation of mesenchymal stem cells (MSC) has been proposed to improve wound healing. However, as these cells only transiently survive in the implantation site, the mechanisms underlying this beneficial healing response are associated with restorative paracrine effects of MSC matricellular factors on resident stromal cells. However, this requires that the recipient has a robust reservoir of viable cells. Here, we examine the influence of MSCs on the behavior of cotransplanted fibroblasts, in a manner to provide augmented cellular reserve to debilitated individuals, specifically focusing on matrix remodeling following in-vivo wounding.MethodsUsing a Hylan-A dermal filler hydrogel containing collagen I and tenascin-C for delivery and increased survival of transplanted cells, we find that cotransplantation of MSCs with fibroblasts reduces scarring.ResultsTransplanted xenogeneic MSCs augmented fibroblast proliferation, migration, and extracellular matrix deposition critical for wound closure, and reduced inflammation following wounding. MSCs also corrected matrix remodeling by CXCR3-deficient fibroblasts which otherwise led to hypertrophic scarring. This effect was superior to MSC or fibroblast transplantation alone.ConclusionsTaken together, these data suggest that MSCs, even if eventually rejected, transplanted with fibroblasts normalize matrix regeneration during healing. The current study provides insight into cellular therapies as a viable method for antifibrotic treatment and demonstrates that even transiently engrafted cells can have a long-term impact via matrix modulation and education of other tissue cells.

Amino acid-insensitive mTORC1 regulation enables nutritional stress resilience in hematopoietic stem cells.

The mTOR pathway is a critical determinant of cell persistence and growth wherein mTOR complex 1 (mTORC1) mediates a balance between growth factor stimuli and nutrient availability. Amino acids or glucose facilitates mTORC1 activation by inducing RagA GTPase recruitment of mTORC1 to the lysosomal outer surface, enabling activation of mTOR by the Ras homolog Rheb. Thereby, RagA alters mTORC1-driven growth in times of nutrient abundance or scarcity. Here, we have evaluated differential nutrient-sensing dependence through RagA and mTORC1 in hematopoietic progenitors, which dynamically drive mature cell production, and hematopoietic stem cells (HSC), which provide a quiescent cellular reserve. In nutrient-abundant conditions, RagA-deficient HSC were functionally unimpaired and upregulated mTORC1 via nutrient-insensitive mechanisms. RagA was also dispensable for HSC function under nutritional stress conditions. Similarly, hyperactivation of RagA did not affect HSC function. In contrast, RagA deficiency markedly altered progenitor population function and mature cell output. Therefore, RagA is a molecular mechanism that distinguishes the functional attributes of reactive progenitors from a reserve stem cell pool. The indifference of HSC to nutrient sensing through RagA contributes to their molecular resilience to nutritional stress, a characteristic that is relevant to organismal viability in evolution and in modern HSC transplantation approaches.

Factors Regulating Stem Cell Biology in Development and Disease.

Stem cells in general are characterized by their ability to self-renew and to differentiate towards various progeny. Great efforts started to give hope since the first discovery of mammalian pluripotency by Stevens and Little, 1954; the field of stem cell research using pluripotent stem cells (PSC) has reached a state of general interest in both science and medicine. Following an overall fast development of in vivo and in vitro research, stem cells are nowadays regularly implied in developmental and pathomechanistical studies. Their unique ability to generate all cell types of the respective organism allows for the directed differentiation of in vitro cultured PSCs into the desired direction. Subsequently, development and function of this differentiated progeny may be investigated in detail. This specifically accounts for the human system where primary materials as well as in vivo studies are strongly limited. In addition, the groundbreaking study describing the generation of PSCs from somatic cells by Takahashi and Yamanaka, served as a lift for unlimited use of individual and patient specific stem cell based investigations. Today, these induced pluripotent stem cells (iPSCs) are amongst others utilized to explicitly study human pathomechanisms in a patient specific setting. Moreover, tissue specific stem cell, for example, serving as a cellular reserve and substitute for decayed cells and degenerated tissue, is discussed as a useful source of human tissue and tissue specific cells. Clearly, these adult stem cells have already been successfully used in therapeutic approaches for decades, such as hematopoietic stem cells in bone marrow transplantations.

Auxin signal transduction into a quantitative change in natural auxin polar transport in pine cambium

Results of experiments performed with 6-mm high stem sections of &lt;em&gt;Pinus sylvestris&lt;/em&gt; L. confirmed the hypothesis that the fusiform cells of the cambial region respond to the arrival of indole-3-acetic-acid (IAA) at the signalling concentration in the apoplastic space around their apical ends by increasing the basipetal efflux of endogenous natural auxin. Thus, the auxin signal propagation along the stem cambial region could be a chain of reactions between the axially neighbouring cells, each capable of responding and contributing to the change of auxin concentration in the apoplast which requires only transduction of the foreign auxin signal by each of the cells to increase the basipetal efflux of their own endogenous auxin. The rate of auxin signal propagation in this system is not limited by the rate of auxin molecular transport, and if it functions in conjunction with feedback inhibition, it may produce oscillations of the auxin basipetal efflux generating supracellular auxin waves. Inhibitors of the proteinaceous auxin efflux carrier associated with the plasmalemma (NPA and TIBA), although reducing total basipetal transport of the natural auxin, did not prevent the stimulated additional efflux of this phytohormone. The studied auxin-signal transduction processes seem to be intracellular but not mediated by the Ca-calmodulin complex. The natural auxin basipetal efflux increased significantly within 45 min following the period when it had been strongly reduced by successive collections to agar receivers replaced several times at the basal ends of 6-mm high stem sections in which the intact fusiform cells of the cambial region in about 90% are arranged in only one axial row. Such exhaustion of the cellular reserve of auxin did not prevent the additional auxin basipetal efflux stimulated by the IAA apical treatment. The results may suggest an effect of the auxin signal upon the supply of newly-synthesised auxin directly to the system responsible for its basipetal efflux.

Neoechinulin A Imparts Resistance to Acute Nitrosative Stress in PC12 Cells: A Potential Link of an Elevated Cellular Reserve Capacity for Pyridine Nucleotide Redox Turnover with Cytoprotection

Treatment of PC12 cells with fungus-derived alkaloid neoechinulin A for more than 12 h renders the cells resistant to subsequent superoxide (O₂⁻)/nitric oxide (NO) insults derived from 3-morpholinosydnonimine (SIN-1). However, the underlying mechanism(s) remains largely unclear. To elucidate the mechanism(s), we assessed the specificity of the cytoprotection afforded by neoechinulin A treatment using other cytocidal stressors and also clarified the resulting cellular alterations, focusing on the antioxidant and metabolic enzymes systems. Neoechinulin A treatment for more than 12 h endowed PC12 cells with significant resistance to transient NO toxicity, but not persistent NO toxicity, bolus H₂O₂ toxicity, or oxidative insult from the redox cycling quinone menadione. Cellular antioxidant system profiling revealed no substantial potentiation of the activity of any antioxidant enzyme in lysate from the neoechinulin A-treated cells excluding glutathione (GSH) content, which was significantly decreased (>50%), resulting in a proportional compromise in the thiol-reducing activity of the intact cells. In addition, no differences were observed in the activity for any nicotinamide adenine dinucleotide (phosphate) reduced form (NAD(P)H)-generating enzyme, steady-state NAD(P)H/nicotinamide adenine dinucleotide (phosphate) oxidized form (NAD(P)⁺) ratios, or the levels of total NAD(P)H. Nevertheless, the neoechinulin A-treated intact cells exhibited increased NAD(P)H redox turnover when driven by extracellular tetrazolium. The structurally inactive analog preechinulin failed to protect cells against NO toxicity or induce these alterations, suggesting their link with the cytoprotective mechanism. These results suggest that neoechinulin A, despite disabling the GSH defense system, confers cytoprotection against nitrosative stresses by elevating the cellular reserve capacity for NAD(P)H generation, which could offset crippling of energy-supplying systems due to nitrosative stress.

Are there errors in glycogen biosynthesis and is laforin a repair enzyme?

Glycogen, a branched polymer of glucose, is well known as a cellular reserve of metabolic energy and/or biosynthetic precursors. Besides glucose, however, glycogen contains small amounts of covalent phosphate, present as C2 and C3 phosphomonoesters. Current evidence suggests that the phosphate is introduced by the biosynthetic enzyme glycogen synthase as a rare alternative to its normal catalytic addition of glucose units. The phosphate can be removed by the laforin phosphatase, whose mutation causes a fatal myoclonus epilepsy called Lafora disease. The hypothesis is that glycogen phosphorylation can be considered a catalytic error and laforin a repair enzyme.

Abstract 122: Mitochondrial dysregulation and cellular death resistance in response to genotoxic stress

Abstract Cellular death resistance is at the foundation of neoplastic progression. Our objective is to identify mechanisms by which genotoxin exposure of normal human cells may lead to intrinsic alterations allowing for selection of survivors with a growth-advantaged phenotype. Certain forms of hexavalent chromium [(Cr(VI)] are human respiratory carcinogens/oxidizing agents. We have generated populations of BJ-hTERT fibroblasts (stably transfected with the telomerase gene), which have acquired resistance to Cr(VI)-induced death, that was not related to DNA adduct formation. In the present study, subclones were derived from clonogenic survivors of BJ-hTERT cells treated with either 0 µM (CC) or a single exposure to 5 µM (DR1 and DR2) Cr(VI). We investigated caspase 3 cleavage in these lines after 24 h exposure to Cr(VI). CC cells exhibited a &amp;gt;70 fold increase in cleaved caspase 3 expression after Cr(VI) treatment, accompanied by substantial release of mitochondrial cytochrome c, consistent with induction of the mitochondrial apoptosis pathway. In sharp contrast, DR1 and DR2 cells showed significant resistance to Cr(VI)-induced caspase 3 cleavage, which was ∼10 fold increase as compared to control, and Cr(VI)-induced cytochrome c release was negligible. Apoptotic resistance was not related to differences in either hTERT or p53 protein levels, which were similar among the cell lines before and after Cr(VI) treatment. We next investigated potential intrinsic mitochondrial alterations that may contribute to the observed apoptosis resistant phenotype. We measured mitochondrial (mt) DNA copy number by RT-PCR of the mtND1 gene, and found no difference among the cell lines, before or after Cr(VI) treatment. Notably, mtDNA is highly susceptible to oxidative damage. Amplification of an 8.9 kb mtDNA product has been shown to be inversely proportional to mtDNA damage. Intriguingly, our data show that the CC cells display 10-20% less amplifiable mtDNA, as compared to the DR cells (reaching statistical significance in DR1), with no effect of Cr(VI) treatment. Mitochondrial spare respiratory capacity (SRC) has been associated with maintenance of a cellular energy reserve in the face of oxidative stress. We measured basal SRC in the CC and DR cells after injection of 1.5 µM FCCP, a respiratory chain uncoupler. Of note, DR1 and DR2 cells showed a significant, ∼2-fold increase in oxygen consumption rate (OCR) as compared to CC cells, with no difference in basal OCR. Taken together, these data indicate that DR cells have both decreased mtDNA damage and increased SRC, which may be related to their intrinsic death resistance. In conclusion, our data suggest that cell survival after a single genotoxic insult involves the selection of cells with intrinsic mitochondrial dysregulation, leading to death resistance, which may play a role in neoplastic progression. Supported by NIH grants CA107972 to SC and supplement to KW, ES05304 and ES09961 to SRP. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 122.

Adenomatous polyposis coliregulatesDrosophilaintestinal stem cell proliferation

Adult stem cells define a cellular reserve with the unique capacity to replenish differentiated cells of a tissue throughout an organism's lifetime. Previous analysis has demonstrated that the adult Drosophila midgut is maintained by a population of multipotent intestinal stem cells (ISCs) that resides in epithelial niches. Adenomatous polyposis coli (Apc), a tumor suppressor gene conserved in both invertebrates and vertebrates, is known to play a role in multiple developmental processes in Drosophila. Here, we examine the consequences of eliminating Apc function on adult midgut homeostasis. Our analysis shows that loss of Apc results in the disruption of midgut homeostasis and is associated with hyperplasia and multilayering of the midgut epithelium. A mosaic analysis of marked ISC cell lineages demonstrates that Apc is required specifically in ISCs to regulate proliferation, but is not required for ISC self-renewal or the specification of cell fate within the lineage. Cell autonomous activation of Wnt signaling in the ISC lineage phenocopied Apc loss and Apc mutants were suppressed in an allele-specific manner by abrogating Wnt signaling, suggesting that the effects of Apc are mediated in part by the Wnt pathway. Together, these data underscore the essential requirement of Apc in exerting regulatory control over stem cell activity, as well as the consequences that disrupting this regulation can have on tissue homeostasis.

Growth of Pleurotus ostreatus on wheat straw and wheat-grain-based media: biochemical aspects and preparation of mushroom inoculum

Mycelial growth, intracellular activity of proteases, laccases and beta-1,3-glucanases, and cytoplasmic protein were evaluated in the vegetative phase of Pleurotus ostreatus grown on wheat straw and in wheat-grain-based media in Petri dishes and in bottles. The productivity of the wheat straw and wheat-grain-based spawn in cylindrical polyethylene bags containing 5 kg of chopped straw was also determined. We observed high activity of proteases and high content of intracellular protein in cultures grown on wheat straw. This suggests that the proteases are not secreted into the medium and that the protein is an important cellular reserve. On the contrary, cultures grown on wheat straw secreted laccases into the medium, which could be induced by this substrate. P. ostreatus grown on media prepared with a combination of wheat straw and wheat grain showed a high radial growth rate in Petri dishes and a high level of mycelial growth in bottles. The productivities of wheat straw and wheat-grain-based spawn were similar. Our results show that cheaper and more productive mushroom spawn can be prepared by developing the mycelium on wheat straw and wheat-grain-based substrates.

INCREASED ENDOTHELIN-1 PRODUCTION DURING COLD ISCHEMIA IN STEATOTIC AND NONFUNCTIONAL HUMAN LIVER ALLOGRAFTS MAY INDICATE ENHANCED SUSCEPTIBILITY TO ISCHEMIA-REPERFUSION INJURY

276 Background/purpose: Early liver graft failure may be related to ischemia-reperfusion injury mediated by a balance of cellular antioxidant protection, cytosolic second messengers, and intracellular toxins such as endothelin 1 (ET-1). ET-1 generated during experimental warm ischemia may potentiate preservation injury via its vasospastic and cholestatic effects. However the role of ET-1 and intracellular reserve in cold ischemic injury is poorly understood for human liver grafts in clinical liver transplantation.Methods: Tissue content of catalase, endothelin-1, and cyclic AMP(cAMP) was measured in five human liver grafts demonstrating excellent post transplant function (Gp, A, n=5) and compared with that in five liver grafts discarded for steatosis and one demonstrating primary nonfunction after transplantation (Gp B, n=6). Samples from each graft were maintained at 4 degrees Centigrade in UW solution for 24 hours immediately after retrieval, and assayed at 6 hour intervals for catalase, endothelin-1, and cyclic AMP.Results: (Table 1). All grafts demonstrated progressive depletion of cAMP and catalase and a time dependent increase in ET-1 during 24 hours of cold preservation. The rate of ET-1 production was significantly higher in Gp B. Despite greater depletion of cAMP in suboptimal grafts (Gp B), the differences between groups were not statistically significant. The rate of loss of catalase activity was not significantly different between the two groups.Conclusions: Intracellular markers may provide an objective estimate of cellular reserve for ischemia-reperfusion events in human liver grafts. An enhanced rate of change in markers such as ET-1 during cold preservation may identify human liver grafts at risk for post transplant dysfunction such as cholestasis and nonfunction.

INCREASED ENDOTHELIN-1 PRODUCTION DURING COLD ISCHEMIA IN STEATOTIC AND NONFUNCTIONAL HUMAN LIVER ALLOGRAFTS MAY INDICATE ENHANCED SUSCEPTIBILITY TO ISCHEMIA-REPERFUSION INJURY

276 Background/purpose: Early liver graft failure may be related to ischemia-reperfusion injury mediated by a balance of cellular antioxidant protection, cytosolic second messengers, and intracellular toxins such as endothelin 1 (ET-1). ET-1 generated during experimental warm ischemia may potentiate preservation injury via its vasospastic and cholestatic effects. However the role of ET-1 and intracellular reserve in cold ischemic injury is poorly understood for human liver grafts in clinical liver transplantation.Methods: Tissue content of catalase, endothelin-1, and cyclic AMP(cAMP) was measured in five human liver grafts demonstrating excellent post transplant function (Gp A, n=5) and compared with that in five liver grafts discarded for steatosis and one demonstrating primary nonfunction after transplantation (Gp B, n=6). Samples from each graft were maintained at 4 degrees Centigrade in UW solution for 24 hours immediately after retrieval, and assayed at 6 hour intervals for catalase, endothelin-1, and cyclic AMP.Results:(Table 1). All grafts demonstrated progressive depletion of cAMP and catalase and a time dependent increase in ET-1 during 24 hours of cold preservation. The rate of ET-1 production was significantly higher in Gp B. Despite greater depletion of cAMP in suboptimal grafts (Gp B), the differences between groups were not statistically significant. The rate of loss of catalase activity was not significantly different between the two groups.Table.1Conclusions: Intracellular markers may provide an objective estimate of cellular reserve for ischemia-reperfusion events in human liver grafts. An enhanced rate of change in markers such as ET-1 during cold preservation may identify human liver grafts at risk for post transplant dysfunction such as cholestasis and nonfunction.

Nutritional Support in the Frail Elderly Surgical Patient

Malnutrition is common in the elderly population, particularly residents living in nursing homes. The decrease in nutrient intake associated with aging reduces cellular function and reserve capacity. Refeeding of malnourished elderly patients prior to elective surgeries, or following emergency surgeries, can reduce surgical morbidity and mortality. A large number of elderly patients become unable to maintain their nutritional status by oral feedings. Modern techniques and materials allow the use of the gastrointestinal tract for nutritional support in most of these patients. The ultimate goal for health care in the 1990s is to provide quality life at home. Nutritional support has become an integral component of home services for the elderly.

Effects of nickel hydroxycarbonate on alveolar macrophage functions.

The metabolic effects of different concentrations of nickel hydroxycarbonate (NiHC) on guinea pig alveolar macrophages (GPAMs) were investigated. Exposure to high concentrations of NiHC (6.25 and 12.5 micrograms 10(-6) cells) led to cell vacuolization. Morphological changes were associated with a dramatic reduction in the steady-state level of cellular adenosine triphosphate (ATP), i.e. ATP levels were reduced by 35% (P less than 0.001) and 53% (P less than 0.01), respectively. Low concentrations of NiHC (0.0625 and 0.125 microgram 10(-6) cells) did not induce morphological changes but increased cellular ATP content by 19% (P less than 0.01) and 12% (P less than 0.05), respectively. Effects of NiHC (0.125 and 6.25 micrograms 10(-6) cells) on cell oxidative metabolism were studied. The chemiluminescence was significantly increased (P less than 0.001) by the lower but not the higher concentration. A slight inhibition of total superoxide dismutase (P less than 0.05) and a decrease of catalase activity were demonstrated (P less than 0.05) for the high dose, while the low dose decreased the levels of reduced and total glutathione. In conclusion, the effects of NiHC on alveolar macrophages are characterized by an overproduction of free radicals for low concentrations and the depletion of cellular reserve energy, particularly ATP, for high concentrations.

Ischemic cardiomyopathy: Pathophysiologic mechanisms

SCHEMIC cardiomyopathy is an anatomic condition emanating from a sustained imbalance between oxygen supply and demand of the heart that, in turn, leads to myocyte loss with resultant myocardial scarring and ventricular failure. Cell loss can occur as a result of focal narrowing or occlusion of the main coronary arteries by atherosclerosis, spasm of the epicardial or intramural branches of the coronary circulation, and alterations of the capillary network, which in an independent or combined fashion create varying degrees of ischemia and tissue injury. These pathologic processes affecting the large, intermediate, and small sized arteries and arterioles, and the capillary microcirculation are responsible for a variety of clinical manifestations. The resulting clinical spectrum ranges from acute myocardial infarction to chronic ischemic cardiomyopathy developing years after initial segmental loss of functioning tissue. The latter may take the form of a dilated congestive ischemic myopathy that is characterized solely by discrete but multiple focal sites of myocardial damage in the ventricular wall. Structural alterations of the myocardium resulting from ischemia-induced tissue injury and their impact on the evolution of the cardiomyopathic heart have been studied experimentally in the last decade in order to elucidate the pathophysiologic events implicated in the onset, development, and progression of congestive heart failure of ischemic origin. This article reviews the quantitative morphological characteristics of the ventricular myocardium in ischemia in an attempt to analyze how both losses in cardiac mass and tissue regeneration by cellular reserve growth mechanisms participate in ventricular wall remodeling and ultimate myocardial dysfunction,

Microbial Metabolism of Quinoline and Related Compounds: I. Isolation and Characterization of Quinoline-Degrading Bacteria

Summary From soil and water samples and from activated sludge of a sewage treatment plant 16 bacterial strains were isolated which utilize quinoline as sole carbon and nitrogen source. The majority of the strains are Gram-negative, aerobic, polarly flagellated rods which do not form spores. They are catalase positive and cytochrome oxidase positive. Some strains can grow anaerobically at the expense of nitrate. Some of them accumulate poly-β-hydroxybutyrate as cellular reserve material. 13 strains could be identified as members of the genus Pseudomonas . Three strains show a positive Gram strain and were identified as Rhodococcus species.