Haemoglobin Bohr effect and lactic acid content of the blood of 2 water-snakes with different degrees of aquatic adaptation

Summary H. modestus, a water-snake with morphological respiratory adaptation to its habitat, presents haemoglobins with a lower Bohr effect than those ofL. miliaris, an aquatic snake without such respiratory adaptations. The difference in blood lactic acid content of the 2 snakes submitted to mechanical stimuli appears to be compatible with the properties of their haemoglobins.Suported in part by FAPESP-Proc. 76/1338     

An improved electrophoretic method for a screening program for haemoglobinopathies

Summary A method for a screening program for haemoglobinopathies in a starch agar gel mixed with saponin is presented. Normal and abnormal blood containing haemoglobins S, C, I, M Boston, D Punjab, beta thalassaemia major and beta thalassaemia minor, were applied, in a tray with the capacity for 100 samples. The electrophoresis was performed in 45 min using 300 V. This method offers special advantages for the examination of a large number of samples, using a small amount of whole blood and without the previous preparation of haemoglobin solution.Acknowledgments. We would like to express our gratitude to Dr C. Daghlian and Dr Lewis J. Greene for their valuable suggestions. We also thank the Conselho Nacional do Desenvolvimento Científico e Tecnológico, CNPq, for financial support.     

Genetics and molecular pathogenesis of mitochondrial respiratory chain diseases

Dysfunction of the mitochondrial respiratory chain has been recognised as a cause of human disease for over 30 years. Advances in the past 10 years have led to a better understanding of the genetics and molecular pathogenesis of many of these disorders. Over 100 primary defects in mitochondrial DNA (mtDNA) are now implicated in the pathogenesis of a group of disorders which are collectively known as the mitochondrial encephalomyopathies, and which most frequently involve skeletal muscle and/or the central nervous system. Although impaired oxidative phosphorylation is likely to be the final common pathway leading to the cellular dysfunction associated with such mtDNA mutations, the complex relationship between genotype and phenotype remains largely unexplained. Most of the genes which encode the respiratory chain reside in the nucleus, yet only five nuclear genes have been implicated in human respiratory chain diseases. There is evidence that respiratory chain dysfunction is present in common neurological diseases such as Parkinson's disease and Huntington's disease. The precise cause of this respiratory chain dysfunction and its relationship to the disease process are unclear. This review focuses upon respiratory chain disorders associated with primary defects in mtDNA.     

Fenretinide induces mitochondrial ROS and inhibits the mitochondrial respiratory chain in neuroblastoma

Fenretinide induces apoptosis in neuroblastoma by induction of reactive oxygen species (ROS). In this study, we investigated the role of mitochondria in fenretinide-induced cytotoxicity and ROS production in six neuroblastoma cell lines. ROS induction by fenretinide was of mitochondrial origin, demonstrated by detection of superoxide with MitoSOX, the scavenging effect of the mitochondrial antioxidant MitoQ and reduced ROS production in cells without a functional mitochondrial respiratory chain (Rho zero cells). In digitonin-permeabilized cells, a fenretinide concentration-dependent decrease in ATP synthesis and substrate oxidation was observed, reflecting inhibition of the mitochondrial respiratory chain. However, inhibition of the mitochondrial respiratory chain was not required for ROS production. Co-incubation of fenretinide with inhibitors of different complexes of the respiratory chain suggested that fenretinide-induced ROS production occurred via complex II. The cytotoxicity of fenretinide was exerted through the generation of mitochondrial ROS and, at higher concentrations, also through inhibition of the mitochondrial respiratory chain.     

Respiratory control in liver mitochondria of rats hosting the walker 256 carcinoma tumor.

The decrease in the respiratory control ratio of mitochondria is a first order process when these organelles are incubated in isotonic sucrose. Furthermore, the initial respiratory control ratios and the rates of loss in respiratory control in liver mitochondria from rats hosting the Walker 256 carcinoma are not significantly different form the same properties of mitochondria from untreated animals.     

Why do patients with respiratory muscle paralysis require artificial hyperventilation?

Summary The primary reason for the need of hyperventilation in patients with respiratory paralysis is the insufficiency of the inhibitory Hering-Breuer reflex. The artificial distension of the lungs with normal tidal volume cannot inhibit the respiratory centre in contrast to the normal state.     

Why do patients with respiratory muscle paralysis require artificial hyperventilation?

The primary reason for the need of hyperventilation in patients with respiratory paralysis is the insufficiency of the inhibitory Hering-Breuer reflex. The artificial distension of the lungs with normal tidal volume cannot inhibit the respiratory centre in contrast to the normal state.     

Temperature-controlled alternative respiration and outgrowth rate from conidia ofNeurospora crassa

Summary Incubation of conidia of wild typeNeurospora crassa at temperatures ranging from 25 to 46°C modulates their respiratory type. Between 37 and 41°C, the transient activity of the cyanide-insensitive respiratory pathway parallels, with a maximal extrusion of protons into the medium, the optimal rate of germ tube outgrowth.We are grateful to Mrs Arlette Cattaneo for her competent technical assistance.     

Erythropoietin modulates the neural control of hypoxic ventilation

Numerous factors involved in general homeostasis are able to modulate ventilation. Classically, this comprises several kind of molecules, including neurotransmitters and steroids that are necessary for fine tuning ventilation under different conditions such as sleep, exercise, and acclimatization to high altitude. Recently, however, we have found that erythropoietin (Epo), the main regulator of red blood cell production, influences both central (brainstem) and peripheral (carotid bodies) respiratory centers when the organism is exposed to hypoxic conditions. Here, we summarize the effect of Epo on the respiratory control in mammals and highlight the potential implication of Epo in the ventilatory acclimatization to high altitude, as well as in the several respiratory sickness and syndromes occurring at low and high altitude. (Part of a multi-author review.)     

Circulatory and respiratory consequences of massive hemorrhage are reversed by protoveratrines

In a rat model of severe hypotension and respiratory depression induced by step-wise bleeding, protoveratrines cause a prompt and sustained improvement of cardiovascular and respiratory functions, both in anesthetized and in conscious animals, seemingly through a magnification of the reflex response originated by the chemoreceptors of aortic and carotid bodies. The restoration of cardiovascular function is attributable to an increase both in total peripheral resistance and cardiac output. The finding could provide the basis for a new approach to the first-aid management of massive blood losses.     

Circulatory and respiratory consequences of massive hemorrhage are reversed by protoveratrines

Summary In a rat model of severe hypotension and respiratory depression induced by step-wise bleeding, protoveratrines cause a prompt and sustained improvement of cardiovascular and respiratory functions, both in anesthetized and in conscious animals, seemingly through a magnification of the reflex response originated by the chemoreceptors of aortic and carotid bodies. The restoration of cardiovascular function is attributable to an increase both in total peripheral resistance and cardiac output. The finding could provide the basis for a new approach to the first-aid management of massive blood losses.     

The effects of 4 detergents on the respiration of mitochondria isolated from rat liver]

The effects of these four detergents (two non-ionic: Titron X100 and Tween 80, two ionic: sodium cholate and sodium dedeoxycholate) upon the respiratory intensities of mitochondria and upon the ADP/0 and respiratory control ratios were observed. At low concentrations and in the absence of exogenous ADP, non ionic as well as ionic detergents provoked a threefold (or fourfold) increase of the respiratory intensities of mitochondria. At higher concentrations, the four detergents were inhibitory for mitochondrial oxidations in the order: Triton X 100 greater than DOC greater than cholate greater than Tween 80. At increasing doses, the four detergents progressively decreased the phosphorylating capacities of mitochondria.     

Importance of respiratory route in experimental salmonellosis in Balb/c mice]

Infection of Mice with S. typhimurium, was conducted by respiratory, oral and peritoneal routes. The results obtained showed that infection occurred more quickly by i. p. than by other routes. However i. n. inoculation is the more efficient concerning Bacteria concentration per Mousse to obtain the DL 100. A study of Salmonella growth in vivo was conducted in lungs, spleen, liver and blood. The results are discussed in relation to the calf respiratory Salmonellosis actually observed.     

Breathing at high altitude

Acclimatization to long-term hypoxia takes place at high altitude and allows gradual improvement of the ability to tolerate the hypoxic environment. An important component of this process is the hypoxic ventilatory acclimatization (HVA) that develops over several days. HVA reveals profound cellular and neurochemical re-organization occurring both in the peripheral chemoreceptors and in the central nervous system (in brainstem respiratory groups). These changes lead to an enhanced activity of peripheral chemoreceptor and re-inforce the central translation of peripheral inputs to efficient respiratory motor activity under the steady low O₂ pressure. We will review the cellular processes underlying these changes with a particular emphasis on changes of neurotransmitter function and ion channel properties in peripheral chemoreceptors, and present evidence that low O₂ level acts directly on brainstem nuclei to induce cellular changes contributing to maintain a high tonic respiratory drive under chronic hypoxia. (This study is part of a multi-author review.)     

Priming effect of vasoactive intestinal peptide on the respiratory burst of neutrophils non-mediated by plasma membrane receptors

Vasoactive intestinal peptide (VIP) primed the respiratory burst of human neutrophils in response to phorbol myristate acetate. Maximal and half-maximal effects were achieved at 10 and 0.5 nM VIP respectively. The absence of plasma membrane receptors to VIP in neutrophils suggests that priming of the respiratory burst should be considered as a side effect of VIP. However, from the above indicated concentration range, the priming of the neutrophil by VIP cannot be considered as a pharmacological effect. The enhancement of the formation of reactive oxygen metabolites by VIP may be important in the pathology of VIP-producing tissues.     

Impaired metabolism of arachidonate in selenium deficient animals

Cellular and Molecular Life Sciences - Arachidonate-induced respiratory distress in mice was aggravated in a selenium deficient group as compared with a selenium supplemented one. The aggravation...     

Respiratory inhibition and reversible fusion of frog blastomeres.

Rotenone and high doses of chloramphenicol, both of which specifically inhibit electron transport between NADH and flavoprotein in the respiratory chain, caused fully separated Rana pipiens blastomeres to refuse, as shown by syncytium counts on embryos reconstructed from serial sections. With chloramphenicol, the effect was completely reversible: re-cleavage and normal development followed drug removal. The blastomere fusion effect was not produced by the succinic dehydrogenase-specific respiratory inhibitor, thenoyltrifluoroacetone, nor by a non-mitochondrial protein synthesis inhibitor, cycloheximide, both of which instead produced simple arrest of cleavage.     

Adaptive respiratory variation in 4 chromosomal species of mole rats

Oxygen and carbon dioxide pressures were measured in subcutaneous gas pockets of 4 chromosomal species of the Spalax ehrenbergi complex. Oxygen pressures of 11.8, 13.6, 16.9, and 17.2 torr and CO2 pressures of 84.2, 82.9, 80.1, and 64.1 torr were measured for the chromosomal species 2n = 52, 54, 58, and 60, respectively. The differences between the 4 chromosomal species in their subcutaneous gas tension appear to reflect adaptive respiratory variation associated with geographic variation in climate. It underlies an important respiratory physiological correlate of ecological speciation in the extremely hypoxic and hypercapnic subterranean environment.     

Permeability of rat heart myocytes to cytochrome c

Rat heart myocytes undergoing progressive damage demonstrate morphological changes of shortening and swelling followed by the formation of intracellular vacuoles and plasma membrane blebbing. The damaged myocytes displayed impaired N,N'-tetramethyl-p-phenyldiamine (TMPD) ascorbate-stimulated respiratory activity which was restored by the addition of reduced cytochrome c to the cell culture medium. To clarify the role played by cytochrome c in the impairment of cell respiration, polarographic, spectrophotometric and fluorescence as well as electron microscopy imaging experiments were performed. TMPD/ascorbate-stimulated respiratory activity returned to control levels, at approximately 20 microM cytochrome c, establishing the threshold below which the turnover rate by cytochrome c oxidase in the cell depends on cytochrome concentration. Mildly damaged cardiac myocytes, as indicated by cell shortening, retention of visible striations and free-fluorescein exclusion, together with the absence of lactate dehydrogenase leakage and exclusion of trypan blue, were able to oxidize exogenous cytochrome c and were permeable to fluorescein-conjugated cytochrome c. The results, while consistent with an early cytochrome c release observed at the beginning of cell death, elucidate the role played by cytochrome c in the kinetic control of mitochondrial electron transfer under pathological conditions, particularly those involving the terminal part of the respiratory chain. These data are the first to demonstrate that the sarcolemma of cardiac myocytes, damaged but still viable, is permeable to cytochrome c.