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Modification in the ppk gene of Helicobacter pylori during single and multiple experimental murine infections.

The bacterial pathogen Helicobacter pylori is highly adapted to the human stomach, and a high level of polymorphism is observed among clinical isolates. This polymorphism may be the consequence of adaptive changes during colonization, making a strain better able to survive, to evade the immune system, and to provoke a chronic infection. To investigate the mechanisms involved in the acquisition of diversity in H. pylori, mouse models of single infections, coinfections, and superinfections were developed. These experimental infections were conducted with strain SS1, well known to be mouse adapted, and with two strains freshly isolated from infected patients: Hp141 and Hp145. Genetic modifications occurring in these strains were studied over time by comparing randomly selected colonies of the emerging strains to those of the infecting strains by using randomly amplified polymorphic DNA fingerprinting with six different primers and by using PCR to amplify the vacA and cagA genes. We showed that, regardless of the number of infecting strains, only one emerged from the animals and that the establishment of a first strain thwarted the implantation of a second strain. During both a single infection and a coinfection with SS1, Hp141 was replaced by a genetic variant (Hp141v) that overcame SS1 in coinfection experiments. Hp141v exhibited a deletion of a 102-bp repeated sequence within the ppk gene, which encodes polyphosphate kinase (PPK), an enzyme involved in the physiological adaptation of the microbial cell to nutritional and environmental stresses. The deletion led to higher enzymatic activity of PPK, and the variant exhibited a better capacity to colonize mice. Considering that the modified gene is known to be involved in adaptation to a new environment, our results are consistent with an adaptive change in strain Hp141 and suggest that PPK is an important virulence factor in H. pylori.

Adaptation, Physiological↗

Metabolic adaptations of overwintering European common lizards (Lacerta vivipara).

The European common lizard Lacerta vivipara, a reptile of cold-temperate climates, provides us an interesting model of low-temperature adaptation. Indeed its unique cold-hardiness strategy, which employs both freeze tolerance and freeze avoidance, may be seen as the primary reason for its large distribution, which extends from Spain to beyond the Arctic circle. To study the metabolism supporting this capacity, we used three techniques: two techniques of calorimetry (oxygen consumption and thermogenesis) and nuclear magnetic resonance spectroscopy. These techniques were used to examine the metabolic balance and the different molecular pathways used between three different periods through the year (September, January, and May). The results show a significant 20% augmentation of winter anaerobic metabolism compared to other periods of the year. This is mainly because of an activation of the lactic fermentation pathway leading to an increase of lactate concentration (>34% in winter). Furthermore, glucose, which increases some 245% in winter, is used as antifreeze and metabolic substrate. Furthermore, this study provides evidence that the physiological adaptations of the common lizard differ from those of other ectotherms such as Rana sylvatica. Concentrations of alanine and glycerol, commonly used as antifreeze by many overwintering ectotherms, do not increase during winter.

Adaptation, Physiological↗

Changes in free amino acid synthesis in the perfused liver of an air-breathing walking catfish, Clarias batrachus infused with ammonium chloride: a strategy to adapt under hyperammonia stress.

The changes in the free amino acid (FAA) levels, the rate of efflux of FAAs from the perfused liver, and the activity of some enzymes related to amino acid metabolism such as glutamate dehydrogenase (GDH, both reductive amination and oxidative deamination), glutamine synthetase (GS), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) were studied in the liver of a freshwater air-breathing teleost, the walking catfish, Clarias batrachus, perfused with 5 and 10 mM NH(4)Cl. The level of the various non-essential FAAs increased significantly, with a total increase of about 150%, which was accompanied by a significant increase of both ammonia and urea-N in the perfused liver both with 5 and 10 mM NH(4)Cl. The rate of efflux of these non-essential FAAs from the perfused liver also increased significantly with a total increase of about 115% and 160% at 5 and 10 mM NH(4)Cl, respectively. The activity of the mentioned amino acid metabolism-related enzymes in the perfused liver also got stimulated, except for GDH in the ammonia forming direction and ALT, under a higher ammonia load. The activity (both tissue and specific) of GDH in the glutamate forming direction increased maximally, followed by AST and GS in a decreasing order. Owing to these physiological adaptive strategies related to amino acid metabolism along with the presence of a functional and regulatory urea cycle (reported earlier), it is believed that this catfish is able to survive in very high ambient ammonia or in the air or in the mud during habitat drying.

Adaptation, Physiological↗

Comparison of serum creatinine, uric acid, albumin and glucose in male professional endurance athletes compared with healthy controls.

Owing to considerable physical, endocrinological and metabolic adaptations, the analysis of biochemical data in elite and top-class athletes requires caution. With the aim to identify metabolic and biochemical adaptations to particular lifestyle conditions, such as regular and strenuous physical exercise, we measured the concentration of serum albumin, creatinine, uric acid and glucose in 80 male professional cyclists, 37 male members of the Italian national cross-country ski team and 60 male healthy sedentary controls at rest. At variance with earlier investigations, endurance athletes showed significantly decreased concentrations of serum creatinine (controls: 83.1+/-11.0 micromol/l; skiers: 78.0+/-8.4 micromol/l; p<0.05; cyclists: 73.8+/-10.4 micromol/l; p<0.01), uric acid (controls: 362+/-69 micromol/l; skiers: 331 +/-70 micromol/l; p<0.05; cyclists: 312+/-61 micromol/l; p<0.01) and glucose (controls: 5.35+/-0.54 mmol/l; skiers: 4.94+/-0.41 mmol/l; p<0.01; cyclists: 4.94+/-0.42 mmol/l; p<0.01). The concentration of serum albumin was also decreased in athletes, but the difference did not reach statistical significance (controls: 4.76+/-0.26 g/l; skiers: 4.71+/-0.22 g/l; p=0.384; cyclists: 4.68+/-0.22 g/l; p=0.393). Results of the present investigation demonstrate that values of laboratory testing lying outside conventional reference limits calculated on sedentary populations might express physiological adaptations to regular and demanding physical aerobic activity, emphasizing the need for the estimation of reliable reference limits in elite and professional athletes, to avoid equivocal interpretation of results within clinical and anti-doping contests.

Adaptation, Physiological↗

Motor practice and neurophysiological adaptation in the cerebellum: a positron tomography study.

We have used positron tomography (PET) to demonstrate that some parts of the motor system exhibit physiological adaptation during the repeated performance of a simple motor task, but others do not. In contrast to the primary sensori-motor cortex, the cerebellum exhibits a decrease in physiological activation (increases in regional blood flow during performance) with practice. A new application of factorial experimental design to PET activation studies was used to make these measurements in four normal males. This design allowed adaptation to be examined by testing for an interaction between regional cerebral blood flow (rCBF) increases brought about by a motor task and the number of trials (time). These findings are interpreted as the neurophysiological correlates of synaptic changes in the cerebellum associated with motor learning in man.

Adaptation, Physiological↗

Selected Contribution: Improved anoxic tolerance in rat diaphragm following intermittent hypoxia.

Intermittent hypoxia (IH), associated with obstructive sleep apnea, initiates adaptive physiological responses in a variety of organs. Little is known about its influence on diaphragm. IH was simulated by exposing rats to alternating 15-s cycles of 5% O2 and 21% O2 for 5 min, 9 sets/h, 8 h/day, for 10 days. Controls did not experience IH. Diaphragms were excised 20-36 h after IH. Diaphragm bundles were studied in vitro or analyzed for myosin heavy chain isoform composition. No differences in maximum tetanic stress were observed between groups. However, peak twitch stress (P < 0.005), twitch half-relaxation time (P < 0.02), and tetanic stress at 20 or 30 Hz (P < 0.05) were elevated in IH. No differences in expression of myosin heavy chain isoforms or susceptibility to fatigue were seen. Contractile function after 30 min of anoxia (95% N2-5% CO2) was markedly preserved at all stimulation frequencies during IH and at low frequencies after 15 min of reoxygenation. Anoxia-induced increases in passive muscle force were eliminated in the IH animals (P < 0.01). These results demonstrate that IH induces adaptive responses in the diaphragm that preserve its function in anoxia.

Adaptation, Physiological↗

Effect of myocardial ischaemia on left ventricular function and adaptability to exercise training.

PURPOSE: We evaluated the possible interaction between exercise-induced myocardial ischemia and abnormalities in left ventricular function in 72 patients with coronary artery disease at entry and upon discharge from a 6-month exercise training program. METHODS: Twenty-two patients with myocardial ischemia (MIS) defined by electrocardiographic and radionuclide imaging criteria constituted our experimental group (EG). Fifty patients without MIS were assigned to the control group for exercise training (CG-ET) and 31 healthy subjects to the control group for measures of left ventricular function (CG-LV). RESULTS: Both groups EG and CG-ET showed significant and comparable increases in peak oxygen uptake (EG: 25.2 +/- 5.1 to 26.9 +/- 5.4 mL x kg(-1) x min(-1), P < 0.02; CG-ET: 25.1 +/- 0.6 to 27.4 +/- 0.7 mL x kg(-1) x min(-1), P < 0.001) after exercise training, but only CG-ET showed significant reductions in heart rate, systolic blood pressure, and rate-pressure product during submaximal exercise. A significant increase in end-diastolic volume contributed to the increase in cardiac output during exercise in patients with MIS. Heart rate or treadmill time at onset of ST segment depression failed to increase as a result of training, and stroke counts and the product of stroke counts and heart rate showed a trend toward a decrease in response to exercise, suggesting progression of disease. CONCLUSIONS: Patients with myocardial ischemia showed improvements in maximal exercise capacity but failed to elicit physiologic adaptations during submaximal exercise or to increase the threshold for ischemia after exercise training. It is possible that the main emphasis in the management of this type of patient in a cardiac rehabilitation setting should be placed more on coronary risk factor modification to slow progression of disease than on improving cardiovascular efficiency.

Adaptation, Physiological↗

Rate adaptive atrial pacing in the bradycardia tachycardia syndrome.

In 42 patients (26 men, 16 women; mean age 69 +/- 10 years), who were paced and medicated with antiarrhythmic drugs for the bradycardia tachycardia syndrome, chronotropic response and AV conduction with rapid atrial pacing during exercise were studied. Patients were included if they had no second- or third-degree AV block, no complete bundle branch or bifascicular block, and a PQ interval < or = 240 ms during sinus rhythm at rest. The interval between the atrial spike and the following Q wave (SQ) was measured in the supine position at rest with an AAI pacing rate of 5 beats/min above the sinus rate (SQ-R + 5), and at the end of exercise with 110 beats/min (SQ-E110). Bicycle ergometry was performed using the Chronotropic Assessment Exercise Protocol with the pacemakers being programmed to AAI with a fixed rate of 60 beats/min. Chronotropic incompetence was defined as peak exercise heart rate: (1) < 100 beats/min; (2) < 75% of the maximum predicted heart rate; or (3) the heart rate at half the maximum workload < 60 + 2 beats/min per mL O2/kg per minute (calculated O2 consumption). During exercise, one patient developed atrial fibrillation. Chronotropic incompetence was present in 71% (29/41) of the patients according to definition 2, and in 76% (31/41) according to definition 1 or 3. Ten out of 41 patients (24%) exhibited a second-degree AV block with atrial pacing at 110 beats/min at the end of exercise. Only 9 out of the remaining 31 patients (29%) showed a physiological adaptation of the SQ-E110, and 21 patients (68%) exhibited a paradoxical increase of the SQ interval with rapid atrial pacing at the end of exercise as compared to the SQ-R + 5. These observations indicate that the pacing system to be used in most patients paced and medicated for the bradycardia tachycardia syndrome should be dual chamber, and the option of rate adaptation should be considered.

Adaptation, Physiological↗

Cardiorespiratory adaptations induced by aerobic training in middle-aged men: the importance of a decrease in sympathetic stimulation for the contribution of dynamic exercise tachycardia.

We investigated the effects of aerobic training on the efferent autonomic control of heart rate (HR) during dynamic exercise in middle-aged men, eight of whom underwent exercise training (T) while the other seven continued their sedentary (S) life style. The training was conducted over 10 months (three 1-h/sessions/week on a field track at 70-85% of the peak HR). The contribution of sympathetic and para-sympathetic exercise tachycardia was determined in terms of differences in the time constant effects on the HR response obtained using a discontinuous protocol (4-min tests at 25, 50, 100 and 125 watts on a cycle ergometer), and a continuous protocol (25 watts/min until exhaustion) allowed the quantification of the parameters (anaerobic threshold, VO2 AT; peak O2 uptake, VO2 peak; power peak) that reflect oxygen transport. The results obtained for the S and the T groups were: 1) a smaller resting HR in T (66 beats/min) when compared to S (84 beats/min); 2) during exercise, a small increase in the fast tachycardia (delta 0-10 s) related to vagal withdrawal (P < 0.05, only at 25 watts) was observed in T at all powers; at middle and higher powers a significant decrease (P < 0.05 at 50, 100 and 125 watts) in the slow tachycardia (delta 1-4 min) related to a sympathetic-dependent mechanism was observed in T; 3) the VO2 AT (S = 1.06 and T = 1.33 l/min) and VO2 peak (S = 1.97 and T = 2.47 l/min) were higher in T (P < 0.05). These results demonstrate that aerobic training can induce significant physiological adaptations in middle-aged men, mainly expressed as a decrease in the sympathetic effects on heart rate associated with an increase in oxygen transport during dynamic exercise.

Adaptation, Physiological↗

Endogenous oploid peptides stimulate post-exercise insulin response to glucose in rats.

Exercise is associated with profound changes in glucose metabolism and insulin secretion. Endogenous opioid peptides may be involved in these metabolic adaptations. To gain insights into this hypothesis, we studied the effects of the opioid antagonist naloxone on the insulin response to glucose after a 2.5 h exercise bout, either by means of an intravascular glucose tolerance test in male Wistar rats or from rat islets of Langerhans isolated just after exercise. There was a tenfold increase in plasma beta-endorphin concentrations (9.8 +/- 2.1 vs. 114.2 +/- 22.0 fmol/ml, p < 0.001) in animals killed immediately after exercise. The in vivo post-exercise peak insulin response to glucose was markedly reduced compared to resting controls (p < 0.01). Interestingly, naloxone (10 mg/kg) still further decreased the insulin response compared to saline injected exercised rats (p < 0.05), but did not alter the response from resting animals. The post-exercise insulin response to 8.3 mM glucose was significantly reduced compared to resting rat islets (p < 0.05) and was further inhibited when naloxone (10 mu M) was added to the culture medium (p < 0.05). In another experiment, we also tested the effect of 10(-8) and 10(-6) M beta-endorphin on control islets. Both concentrations of beta-endorphin significantly increased the islet insulin response to 8.3 mM glucose (p < 0.05) and this effect was completely blocked by naloxone. These results suggest that endogenous opioid peptides participate in the physiological adaptation to exercise stress in maintaining post-exercise insulin response to glucose.

Adaptation, Physiological↗

Atrial fibrillation in the goat induces changes in monophasic action potential and mRNA expression of ion channels involved in repolarization.

INTRODUCTION: Sustained atrial fibrillation (AF) is characterized by a marked shortening of the atrial effective refractory period (AERP) and a decrease or reversal of its physiologic adaptation to heart rate. The aim of the present study was to investigate whether the AF-induced changes in AERP in the goat are associated with changes in the atrial monophasic action potential (MAP) and whether an abnormal expression of specific ion channels underlies such changes. METHODS AND RESULTS: Following thoracotomy, MAPs were recorded from the free wall of the right atrium both before induction of AF (control) and after cardioversion of sustained AF (>2 months) in chronically instrumented goats. In control goats, MAP duration at 80% repolarization (MAPD80) shortened (P < 0.01) from 132+/-4 msec during slow pacing (400-msec interval) to 86+/-10 msec during fast pacing (180 msec). After cardioversion of sustained AF, the MAPD80 during slow pacing was as short as 67+/-5 msec (electrical remodeling). Increasing the pacing rate resulted in prolongation (P = 0.02) of the MAPD80 to 91+/-6 msec. Also, MAPD20 (20% repolarization) shortened (P = 0.05) from 32+/-4 msec (400 msec) to 14+/-7 msec (180 msec) in the control goats, whereas it prolonged (P = 0.03) from 20+/-3 msec (400 msec) to 33+/-5 msec (180 msec) in sustained AF. mRNA expression of the L-type Ca2+ channel alpha1c gene and Kv1.5 potassium channel gene, which underlie ICa and IKur, respectively, was reduced in sustained AF compared with sinus rhythm by 32% (P = 0.01) and 45% (P < 0.01), respectively. No significant changes were found in the mRNA levels of the rapid Na+ channel, the Na+/Ca2+ exchanger, or the Kv4.2/4.3 channels responsible for Ito. CONCLUSION: AF-induced electrical remodeling in the goat comprises shortening of MAPD and reversal of its physiologic rate adaptation. Changes in the time course of repolarization of the action potential are associated with changes in mRNA expression of the alpha subunit genes of the L-type Ca2+ channel and the Kv1.5 potassium channel.

Action Potentials↗

Changes in tongue and hyoid positions, and posterior airway space following mandibular setback surgery.

INTRODUCTION: The postural response of the tongue after mandibular setback is clinically important for maintaining normal respiration. Although the hyoid bone moves progressively to adapt physiologically to the altered orofacial configuration following such surgery, it is not clear whether repositioning of the hyoid has an effect on the pharyngeal airway. In the present study, postoperative changes in hyoid position and pharyngeal airway space were assessed retrospectively in patients who had undergone mandibular setback surgery. MATERIAL AND METHODS: Digitized lateral cephalograms from 30 mandibular setback surgery cases taken preoperatively, and 1 month and more than 1 year postoperatively, were used to examine pharyngeal airway morphology and the position of hyoid bone. RESULTS: A significant downward movement of the hyoid bone was found 1 month after surgery, while the pharyngeal airway dimensions at the tongue were maintained. More than 1 year after surgery, the hyoid position returned to its original position, resulting in a significant decrease in retrolingual airway dimension. CONCLUSION: The results indicate that mandibular setback causes airway narrowing late after surgery, while the early postoperative airway dimension is maintained. Long-term observations should be performed because of the changes of oropharyngeal configuration following mandibular setback.

Adaptation, Physiological↗

Symposium on 'nutritional adaptation to pregnancy and lactation'. Pregnancy as a time for dietary change?

It is thought that nutrition during pregnancy plays a key role in the well-being of the mother and the newborn infant, and further influences health during childhood and adulthood. Pregnancy is a time of increased nutritional requirements, but many of these requirements will be met by adaptive physiological changes that occur during gestation, with little need to alter maternal dietary intake. A modest increment of food which provides 0.8 MJ/d (above prepregnant requirements) during the third trimester is considered adequate to meet the needs of fetal and maternal growth, and to satisfy the small increase in requirements of many macro- and micronutrients. However, requirements for vitamin D and folic acid increase substantially, and should be met primarily by supplementation. Food selection may also be altered to avoid a range of food-borne diseases and toxic constituents. There are a number of psycho-social reasons why pregnancy might be considered a good time for promoting changes in dietary behaviour for the health of the wider family. However, pregnancy may be a bad time to promote dietary change if it is perceived to involve slimming, if nutritional requirements are greatest before pregnancy, or if dietary changes made are harmful. There is little evidence to support educational interventions as successful at changing dietary behaviour during pregnancy. Pregnancy may be best viewed as an opportunity for maintaining good dietary selections and for building knowledge for future action, and should not be seen as the only opportunity for promoting dietary change within the life course.

Adaptation, Physiological↗

Genetic variance and covariance for physiological traits in Lobelia: are there constraints on adaptive evolution?

Physiological traits that control the uptake of carbon dioxide and loss of water are key determinants of plant growth and reproduction. Variation in these traits is often correlated with environmental gradients of water, light, and nutrients, suggesting that natural selection is the primary evolutionary mechanism responsible for physiological diversification. Responses to selection, however, can be constrained by the amount of standing genetic variation for physiological traits and genetic correlations between these traits. To examine the potential for constraint on adaptive evolution, we estimated the quantitative genetic basis of physiological trait variation in one population of each of two closely related species (Lobelia siphilitica and L. cardinalis). Restricted maximum likelihood analyses of greenhouse-grown half-sib families were used to estimate genetic variances and covariances for seven traits associated with carbon and water relations. We detected significant genetic variation for all traits in L. siphilitica, suggesting that carbon-gain and water-use traits could evolve in response to natural selection in this population. In particular, narrow-sense heritabilities for photosynthetic rate (A), stomatal conductance (gs), and water-use efficiency (WUE) in our L. siphilitica population were high relative to previous studies in other species. Although there was significant narrow-sense heritability for A in L. cardinalis, we detected little genetic variation for traits associated with water use (gs and WUE), suggesting that our population of this species may be unable to adapt to drier environments. Despite being tightly linked functionally, the genetic correlation between A and gs was not strong and significant in either population. Therefore, our L. siphilitica population would not be genetically constrained from evolving high A (and thus fixing more carbon for growth and reproduction) while also decreasing gs to limit water loss. However, a significant negative genetic correlation existed between WUE and plant size in L. siphilitica, suggesting that high WUE may be negatively associated with high fecundity. In contrast, our results suggest that any constraints on the evolution of photosynthetic and stomatal traits of L. cardinalis are caused primarily by a lack of genetic variation, rather than by genetic correlations between these functionally related traits.

Adaptation, Physiological↗

Evidence for a direct role of alpha-MSH in morphological background adaptation of the skin in Sarotherodon mossambicus.

The skin colour of the cichlid teleost Sarotherodon mossambicus adapted rapidly to changes in background colour. The physiological adaptation was associated with morphological changes in the dermis. Differences in the dermis were found between fish adapted to a black or white background for 14 days. Number and size of the melanophores as well as the amount of pigment in the cytoplasm of the melanophores were significantly increased in fish adapted to a black background. Changes in the dermis parallelled changes in the state of activity of the two endocrine cell types in the pars intermedia of the pituitary. Both the PAS positive cells and the MSH producing cells were more active when the fish were exposed to a black rather than a white background. Fish continuously infused with alpha-MSH, using an osmotic minipump, had more melanophore cytoplasm and pigment per dermis surface unit area than untreated fish. The activity of the MSH cells in MSH-infused fish exposed to a black background was reduced to a level comparable to the MSH cell activity of untreated fish on a white background. alpha-MSH treated fish that were exposed to a white background had many disintegrating MSH cells. These findings point to inactivation of these cells by exogenous alpha-MSH. The activity of the PAS positive cells was not influenced by treatment with alpha-MSH.

Acclimatization↗

Functional morphology and physiology of pulmonary rapidly adapting receptors (RARs).

Rapidly adapting receptors (RARs) in the airway mucosa are found from the nasopharynx to the bronchi. They have thin (Adelta) vagal afferent fibres and lie in and under the epithelium, but their morphology has not been defined. They are very sensitive to mechanical stimuli, and have a rapidly adapting irregular discharge. However, with in vitro preparations they are rather insensitive to chemical stimuli, apart from acid and nonisosmolar solutions. Their pattern of response varies with site. RARs in the nasopharynx, larynx, and trachea usually respond only during the onset of stimuli, while those in the trachea often have an off-response as well. Those in the bronchi are less rapidly adapting and more chemosensitive. Their membranes have mechanosensitive and acid-sensitive ion channels, but no vanilloid receptors. In vivo RARs are sensitive to a wide range of chemical irritants and mediators, and presumably are excited secondarily to mechanical changes in the mucosa and airway smooth muscle. In the central nervous system (CNS) they interact with other vagal afferent pathways. The reflexes they cause vary with site (inspiratory efforts from the nasopharynx, cough or expiratory efforts from the larynx and trachea, and deep breaths or tachypnoea from the bronchi). Pathways from RARs and other vagal reflexes show plasticity at the peripheral, ganglionic, and CNS levels.

Adaptation, Physiological↗