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[The present status of conservative therapy in critical lower limb ischemia].

1. Conservative therapy of critical limb ischaemia either supports the effect of revascularisation procedures (thrombolysis, PTA, surgical reconstruction) or is employed in cases where instrumental intervention is no more possible. As a longterm control programme, the conservative approach reduces the number of local and general vascular complications. 2. The main physiological principles of conservative treatment are as follows: improvement of driving pressure (limb dependency, slow walking, mild temporary hypertension induced by isometric contraction of forearm muscles), decrease of vascular resistance (exercise, reflex dilatation by body heating, pharmacological vasodilators, prostanoids), microcirculatory improvement (oxygen inhalation, full recommended doses of drugs), prevention of oedema (calcium blocking agents not to be administered) and prevention of tissue destruction (anabolic hormones). It is of utmost importance to start vigorous therapy without delay when symptoms or signs of incipient critical ischaemia are detected; this should be followed by a life-long control and treatment programme. 3. Early beginning of therapy makes it usually possible to control incipient critical ischaemia effectively. The long term control and treatment programme contributes to a significant drop of relapses and mortality.

Humans↗

Our ancestral physiological phenotype: an adaptation for hypoxia tolerance and for endurance performance?

There are well known mechanistic similarities in human physiology between adaptations for endurance performance and hypoxia tolerance. By using background principles arising from recent studies of the evolution of the diving response in marine mammals, here we analyze human responses to hypobaric hypoxia based on studies with several different low and high altitude human lineages. As in the evolution of the diving response in pinnipeds, we found "conservative" and "adaptable" physiological characters involved in human responses to hypoxia. Because the analysis concerns traits within a single species, conservative characters dominate the picture (they define basic human physiology and largely are independent of environmental parameters). Most notably, we also found evidence for adaptable characters forming the foundations for a fairly unique physiological phenotype-a low capacity version favored under hypobaric hypoxia and a high capacity one favored for endurance performance. Because current evidence implies that the human species arose under conditions that were getting colder, drier, and higher (situations in which these traits would have been advantageous), we hypothesize that this physiology is our "ancestral" condition.

Acclimatization↗

cgh-1, a conserved predicted RNA helicase required for gametogenesis and protection from physiological germline apoptosis in C. elegans.

A high frequency of apoptosis is a conserved hallmark of oocyte development. In C. elegans, about half of all developing oocytes are normally killed by a physiological germline-specific apoptosis pathway, apparently so that they donate cytoplasm to the survivors. We have investigated the functions of CGH-1, the C. elegans ortholog of the predicted RNA helicase ste13/ME31B/RCK/p54, which is germline-associated in metazoans and required for sexual reproduction in yeast. We show that CGH-1 is expressed specifically in the germline and early embryo, and is localized to P granules and other possible mRNA-protein particles. cgh-1 is required for oocyte and sperm function. It is also needed to prevent the physiological germline apoptosis mechanism killing essentially all developing oocytes, making lack of cgh-1 function the first stimulus identified that can trigger this mechanism. We conclude that cgh-1 and its orthologs may perform conserved functions during gametogenesis, that in C. elegans certain aspects of oocyte development are monitored by the physiological germline apoptosis pathway, and that similar surveillance mechanisms may contribute to germline apoptosis in other species.

Amino Acid Sequence↗

Inositol polyphosphate multikinase is a nuclear PI3-kinase with transcriptional regulatory activity.

Phosphatidylinositol 3,4,5-trisphosphate is a major intracellular messenger molecule thought to be formed almost exclusively by cytosolic, wortmannin-inhibited phosphoinositide 3-kinase family members. Inositol polyphosphate multikinase was identified as an enzyme that generates a series of water-soluble inositol phosphates. We now report the robust, physiologic, and evolutionarily conserved phosphoinositide 3-kinase activity of inositol polyphosphate multikinase, which is localized to nuclei and unaffected by wortmannin. In yeast, this inositol lipid kinase activity physiologically regulates transcription.

Androstadienes↗

Surgical versus non-surgical treatment of fractures of the articular process of the mandible.

In a clinical, radiographic and angiographic study, we reinvestigated 34 patients with dislocated fractures of the condylar neck. 20 of them had been treated by open reduction, 14 in a conservative-functional way. The clinical results were nearly equal in both groups. The instrumental registration and the X-ray findings showed considerable deviations in the joint physiology in the conservative group. 19 of 20 patients operated on showed near-anatomical reconstruction with good functional results.

Adolescent↗

Physiological importance of the connective tissue in the human amnion. Role of magnesium.

The elemental ionic distribution in the epithelial layer (EL) and in connective tissue (CT = compact layer + fibroblast layer) of the human amniotic membrane has been studied in reference samples, after conservation in a physiological fluid (Hanks' solution) and after addition of 2 mM MgCl2 in Hanks' solution. Particle induced X-ray emission and Rutherford backscattering spectrometry techniques were used to provide quantitative measurements. In physiological fluid, with regard to reference samples, the monovalent ions (Na+, K +, Cl-) concentrations were identical on both layers. This data indicates that the connective tissue, in particular the compact layer, acts as a buffer which fix minerals. Mg2+ and Ca2+ levels were higher in EL than in CT. The addition of MgCl2 in Hanks' solution induced a decrease of the monovalent ion concentrations in both layers except Na+ level in EL which remained constant, an increase of the Mg2+ level in both layers, while the Ca2+ remained constant. These data indicate the possible role of connective tissue in pregnancies complicated by poly or oligohydramnios.

Amnion↗

The role of energy availability in Mammalian hibernation: a cost-benefit approach.

Hibernation is widely regarded as an adaptation to seasonal energy shortage, but the actual influence of energy availability on hibernation patterns is rarely considered. Here we review literature on the costs and benefits of torpor expression to examine the influence that energy may have on hibernation patterns. We first establish that the dichotomy between food- and fat-storing hibernators coincides with differences in diet rather than body size and show that small or large species pursuing either strategy have considerable potential scope in the amount of torpor needed to survive winter. Torpor expression provides substantial energy savings, which increase the chance of surviving a period of food shortage and emerging with residual energy for early spring reproduction. However, all hibernating mammals periodically arouse to normal body temperatures during hibernation. The function of these arousals has long been speculated to involve recovery from physiological costs accumulated during metabolic depression, and recent physiological studies indicate these costs may include oxidative stress, reduced immunocompetence, and perhaps neuronal tissue damage. Using an optimality approach, we suggest that trade-offs between the benefits of energy conservation and the physiological costs of metabolic depression can explain both why hibernators periodically arouse from torpor and why they should use available energy to minimize the depth and duration of their torpor bouts. On the basis of these trade-offs, we derive a series of testable predictions concerning the relationship between energy availability and torpor expression. We conclude by reviewing the empirical support for these predictions and suggesting new avenues for research on the role of energy availability in mammalian hibernation.

Adipose Tissue↗

Potential role of potassium as a determinant of morbidity and mortality in patients with systemic hypertension and congestive heart failure.

Prehistoric animals and humans consumed a diet low in sodium but high in potassium, and thus, evolutionary forces fostered the development of physiologic systems that conserved sodium and excreted potassium. With the advent of civilized societies, food cooking and processing have greatly increased the sodium but decreased the potassium content of the diet. However, there has been little time for physiologic systems to adapt. The resulting excess of sodium has been implicated as an important factor in the development of hypertension and congestive heart failure. This traditional focus on sodium has ignored the potential role that an inadequate dietary intake of potassium might play in the degenerative diseases of the heart, brain and kidney. Yet dietary potassium may be as powerful a determinant of cardiovascular morbidity and mortality as dietary sodium. In experimental and clinical hypertension, an increased intake of potassium (without a change in dietary sodium) can reduce blood pressure, may suppress the activity of the sympathetic nervous and renin-angiotensin systems, and can prevent the development of vascular injury; conversely, potassium depletion has been associated with an increase in stroke and sudden death. In patients with chronic heart failure, potassium can modify both the mechanical and electrical properties of the heart, it can exert diuretic effects, and it can reduce the frequency and complexity of potentially lethal ventricular tachyarrhythmias. Given this central role, the effects of many pharmacologic interventions on the morbidity and mortality of patients with hypertension or chronic heart failure can be enhanced or diminished by the effect that these treatments might have on potassium homeostasis.(ABSTRACT TRUNCATED AT 250 WORDS)

Heart Failure↗

Biology, ecology, and biotechnological applications of anaerobic bacteria adapted to environmental stresses in temperature, pH, salinity, or substrates.

Anaerobic bacteria include diverse species that can grow at environmental extremes of temperature, pH, salinity, substrate toxicity, or available free energy. The first evolved archaebacterial and eubacterial species appear to have been anaerobes adapted to high temperatures. Thermoanaerobes and their stable enzymes have served as model systems for basic and applied studies of microbial cellulose and starch degradation, methanogenesis, ethanologenesis, acetogenesis, autotrophic CO2 fixation, saccharidases, hydrogenases, and alcohol dehydrogenases. Anaerobes, unlike aerobes, appear to have evolved more energy-conserving mechanisms for physiological adaptation to environmental stresses such as novel enzyme activities and stabilities and novel membrane lipid compositions and functions. Anaerobic syntrophs do not have similar aerobic bacterial counterparts. The metabolic end products of syntrophs are potent thermodynamic inhibitors of energy conservation mechanisms, and they require coordinated consumption by a second partner organism for species growth. Anaerobes adapted to environmental stresses and their enzymes have biotechnological applications in organic waste treatment systems and chemical and fuel production systems based on biomass-derived substrates or syngas. These kinds of anaerobes have only recently been examined by biologists, and considerably more study is required before they are fully appreciated by science and technology.

Adaptation, Physiological↗

Clinical evaluation of a new synthetic protease inhibitor in open heart surgery. Effect on plasma serotonin and histamine release and blood conservation.

To achieve more physiologically successful cardiopulmonary bypass (CPB), the effects of a new synthetic protease inhibitor, nafamostat mesilate (FUT), were examined in open heart surgery. Thirty adult patients were divided into two groups. In Group F (GpF; n = 15), 2 mg/kg/hr of FUT was administered continuously during CPB and 0.2 mg/kg/hr before and after CPB. FUT was not given to Group C patients (GpC; n = 15), who acted as controls. Serotonin and histamine levels in plasma, platelet counts, platelet adhesive function levels, and alpha 2 plasmin inhibitor-plasmin complexes (PIC) were serially measured. The serotonin level in GpF was significantly lower at 5 min of CPB than in GpC. Histamine levels in GpC decreased remarkably after starting CPB, then later recovered; by contrast, they did not decrease in GpF during CPB. At 1 hr after CPB, platelet counts were higher (p < 0.01) in GpF (54 +/- 8%) than in GpC (41 +/- 10%), and platelet adhesion was lower (p < 0.01) in GpF (7 +/- 7%) than in GpC (34 +/- 13%). The PIC was significantly less in GpF than in GpC throughout the surgery. Blood loss in GpF was significantly reduced compared with that in GpC. In conclusion, FUT attenuated chemical mediator reactions, such as plasma serotonin and histamine, and also reduced blood loss by preserving platelets and inhibiting fibrinolysis during CPB.

Adult↗

Energetics of bluetongue lizards (Tiliqua scincoides) in a seasonal tropical environment.

We studied the physiological ecology of bluetongue lizards (Tiliqua scincoides) on the Adelaide River floodplain in tropical Australia to determine the seasonal patterns of energy expenditure and to determine the mechanisms by which seasonal differences were achieved. Field metabolic rates (FMR) were significantly lower in the dry season (37.6 kJ kg(-1) day(-1); n=9) than in the wet (127.3 kJ kg(-1) day(-1); n=7). Water flux was also lower in the dry season (6.8 ml kg(-1) day(-1); n=9) than in the wet (39.4 ml kg(-1) day(-1); n=7). Measurements of body temperatures (T(b)) and movements of free-ranging animals, and standard metabolic rate (SMR) of recently caught animals, allowed a detailed analysis of energy budgets for wet and dry seasons. In the dry, bluetongue lizards expended 90 kJ kg(-1) day(-1) less energy than in the wet season. Unlike some other lizards of the wet-dry tropics, SMR did not differ between seasons. About 5% of the seasonal difference in FMR was due to lower night time T(b) during the dry season, and about 7% was due to lower diurnal T(b). The remaining 88% of the decrease in energy expended in the dry season was due to a substantial decrease in other costs that may include reproduction, growth, digestion and activity. If we assume the animals fed daily and the costs of digestion are taken into account, the estimates are: 14% of the savings result from lower T(b) at night, 20% from lower T(b) in the day, and 66% result from decreased activity. It is therefore apparent that, unlike some agamid and varanid lizards that use a combination of behavioural and physiological mechanisms to conserve energy when food and water are limited, bluetongue lizards primarily use behavioural mechanisms to achieve a dramatic reduction in energy expenditure in the dry season.

Adaptation, Physiological↗

Respiratory properties of cytochrome-c-deficient mutants of Azotobacter vinelandii.

Cytochrome-c-deficient mutants of Azotobacter vinelandii have been isolated following mutagenesis with N-methyl-N'-nitro-N-nitrosoguanidine. These mutants grow well under nitrogen-fixing conditions and studies of the physiology and energy conservation efficiency show no apparent differences from those of the parent strain. Under oxygen-limited growth conditions, the growth rate of the cytochrome-c-deficient mutant was slightly slower (approx. 15%) than that of the parent strain. Cytochromes of the c-type are required for the oxidation of artificial electron donors such as reduced N,N,N',N'-tetramethyl-p-phenylenediamine [Ph(NMe2)2]. This study could not demonstrate a physiological role for the c-type cytochromes which supports the idea that the minor Ph(NMe2)2-oxidizing pathway of the electron transport chain may be independent of the major pathway terminated by cytochrome d.

Azotobacter↗

Amphibian renal disease.

Amphibians by nature have an intimate connection with the aquatic environment at some stage of development and fight an osmotic battle due to the influx of water. Many amphibians have acquired a more terrestrial existence at later stages of development and consequently have physiologic adaptations to conserve moisture. Renal adaptations have allowed amphibians successfully to bridge the gap between aqueous and terrestrial habitats. The kidneys, skin,and, in many amphibian species, the urinary bladder play key roles in fluid homeostasis. Renal impairment may be responsible for the clinical manifestation of disease, morbidity, and mortality.

Adaptation, Physiological↗

Surgical treatment of aortic arch hypoplasia in infants and children with biventricular hearts.

BACKGROUND: Results of aortic arch reconstruction in the setting of biventricular physiology are well documented in the adult population, however, in children, surgical outcome of this subgroup of patients is less clear. METHODS: We studied the clinical outcomes of 37 children aged 8 days to 15 years (median 26 months), who underwent aortic arch reconstruction for arch hypoplasia from 1982 to 1997. The children were divided into three groups: Group 1 (20 patients) had isolated aortic arch lesions, Group 2 (13 patients) had associated intra-cardiac pathology yet conserving a biventricular physiology, Group 3 (4 patients) had Williams Syndrome. Previous interventions for coarctation had been performed in 30 patients (81%). Arch repair consisted of a patch aortoplasty in the majority of patients (35 of 37 children). RESULTS: Operative mortality occurred in 5 children, 4 in Group 2 (31%), 1 in Group 3 (25%) and none in Group 1. Permanent neurological complications occurred in 2 children (5 %). During the follow-up, which ranged from 1 month to 8 years, balloon angioplasty for arch obstruction was required in 1 child. There was one late death, associated with a subsequent intra-cardiac repair. CONCLUSIONS: Aortic arch surgery in children with isolated arch hypoplasia, is associated with excellent early and late survival in addition to a low reintervention rate. Alternative perfusion and operative strategies must be implemented in infants with associated intra-cardiac anomalies to improve results.

Adolescent↗

Marsupial relaxin: complementary deoxyribonucleic acid sequence and gene expression in the female and male tammar wallaby, Macropus eugenii.

The nucleotide and derived amino acid sequences of tammar preprorelaxin were established by combined reverse transcriptase polymerase chain reaction and 3'- and 5'-rapid amplification of cDNA ends methods, using RNA from the corpus luteum of late pregnancy as template. Relaxin gene expression was then investigated in tissues at various stages of the 26-day pregnancy and in adult males. The full-length tammar relaxin preprohormone is 579 base pairs. The derived amino acid sequence contains a probable signal peptide of 26 amino acids, a B-domain of 31 amino acids, a C-domain of 111 amino acids, and an A-domain of 24 amino acids, with sequence homologies of 49%, 38%, 47%, and 47%, respectively, to dogfish, pig, and both human relaxins, for the combined A- and B-domains of the functional peptides. The conserved amino acid residues in the B-domain confirm a region shown to be essential for binding of the peptide to its receptor. A relaxin gene is expressed in several other tissues of pregnant tammars including the placenta, follicle, and hypothalamus. Northern analysis showed a 1-kilobase relaxin transcript in the corpus luteum and placenta. Using RNase protection assays, relaxin gene expression in the corpus luteum was greater in early and mid pregnancy, reduced at term, and absent postpartum. These data demonstrate relaxin biosynthesis in both the corpus luteum and placenta in this marsupial and suggest that a relaxin physiology has been conserved during mammalian evolution.

Amino Acid Sequence↗

Completion of the nucleotide sequence of the 'maltose B' region in Salmonella typhimurium: the high conservation of the malM gene suggests a selected physiological role for its product.

We have subcloned and sequenced the genes malF and malM of Salmonella typhimurium, thereby completing the determination of the nucleotide sequence of its 'maltose B' regulon. The malM gene, encoding a periplasmic protein of unknown function in Escherichia coli, is a highly conserved as genes encoding proteins of known function from the same region.

ATP-Binding Cassette Transporters↗

Molecular and clinical aspects of apoptosis.

Unwanted cells are removed by physiological cell death processes that are highly conserved throughout the animal kingdom. Physiological cell death plays an important role in development, tissue homeostasis and defence against viral infection and mutation. This review describes the molecular components that implement this process, the relevance of these to a variety of human diseases, and discusses the potential for novel therapies based on our understanding of them.

Animals↗

Growth hormone releasing substances: types and their receptors.

A series of structurally diverse growth hormone (GH) releasing substances have been synthesized that are distinct from the naturally occurring GH releasing hormone (GHRH). These synthetic molecules range from the family of GH releasing peptides and mimetics such as MK-0677. The physiological importance of these molecules and their receptor is exemplified by studies in the elderly. For example, when MK-0677 was administered chronically to 70- to 90-year-old subjects, once daily, the age-related reduced amplitude of GH pulses was reversed to that of the physiological profile typical of young adults. In 1996, the synthesis of (35)S-MK-0677 was reported and used as a ligand to characterize a common receptor (GH secretagogue receptor [GHS-R]) for the GH releasing substances. The GHS-R is distinct from the GHRH receptor. Subsequently, the GHS-R gene was cloned and shown to encode a unique G-protein coupled receptor with a deduced protein sequence that was 96% identical in human and rat. Because of the physiological importance of the GHS-R, a search for family members (FMs) was initiated and its molecular evolution investigated. Three FMs GPR38, GPR39 and FM3 were isolated from human genomic libraries. To accelerate the identification of other FMs, a vertebrate organism with a compact genome distant in evolutionary terms from humans was exploited. The pufferfish (Spheroides nephelus) genome provides an ideal model for the discovery of human genes. Three distinct full-length clones encoding proteins of significant sequence identity to the human GHS-R were cloned from the pufferfish. Remarkably, the pufferfish gene with highest sequence homology to the human receptor was activated by the hexapeptide and non-peptide ligands. These intriguing results show that the structure and function of the ligand binding pocket of the human GHS-R has been highly conserved in evolution ( approximately 400 million years) and strongly suggests that an endogenous natural ligand has been conserved. This new information is consistent with a natural ligand for the GHS-R playing a fundamentally important and conserved role in physiology.

Aged↗