A Simple Questionnaire as a First-Step Tool to Detect Specific Frailty Profiles: The Lorraine Frailty-Profiling Screening Scale.

OBJECTIVES: To propose a simple frailty screening tool able to identify frailty profiles. DESIGN: Cross-sectional observational study. SETTING: Participants were recruited in 3 different clinical settings: a primary care outpatient clinic (RURAL population, N=591), a geriatric day clinic (DAY-CLINIC population, N=76) and healthy volunteers (URBAN population, N=147). PARTICIPANTS: A total of 817 older adults (>70 years old) living at home were included. INTERVENTION: A 9-item questionnaire (Lorraine Frailty Profiling Screening Scale, LoFProSS), constructed by an experts' working group, was administered to participants by health professionals. MEASUREMENTS: A Multiple Correspondence Analysis (MCA) followed by a hierarchical clustering of the results of the MCA performed in each population was conducted to identify participant profiles based on their answers to LoFProSS. A response pattern algorithm was resultantly identified in the RURAL (main) population and subsequently applied to the URBAN and DAY-CLINIC populations and, in these populations, the two classification methods were compared. Finally, clinically-relevant profiles were generated and compared for their ability to similarly classify subjects. RESULTS: The response pattern differed between the 3 sub-populations for all 9 items, revealing significant intergroup differences (1.2±1.4 positive responses for URBAN vs. 2.1±1.3 for RURAL vs. 3.1±2.1 for DAY-CLINIC, all p<0.05). Five clusters were highlighted in the main RURAL population: "non-frail", "hospitalizations", "physical problems", "social isolation" and "behavioral", with similar clusters highlighted in the remaining two populations. Identification of the response pattern algorithm in the RURAL population yielded a second classification approach, with 83% of tested participants classified in the same cluster using the 2 different approaches. Three clinically-relevant profiles ("non-frail" profile, "physical frailty and diseases" profile and "cognitive-psychological frailty" profile) were subsequently generated from the 5 clusters. A similar double classification approach as above was applied to these 3 profiles revealing a very high percentage (95.6%) of similar profile classifications using both methods. CONCLUSION: The present results demonstrate the ability of LoFProSS to highlight 3 frailty-related profiles, in a consistent manner, among different older populations living at home. Such scale could represent an added value as a simple frailty screening tool for accelerated and better-targeted investigations and interventions.

Lactate metabolism and glucose turnover in the subterranean crustacean niphargus virei during post-hypoxic recovery

Glucose and lactate metabolism were studied in a hypoxia-resistant subterranean crustacean, Niphargus virei, using an injection of l-[U-14C]lactate and tracer d-[6-3H]glucose either in normoxic conditions or after a 24 h exposure to severe hypoxic. Post-hypoxic animals (H animals) were compared with two treatment groups of normoxic animals. In the first normoxic group (NLL animals), animals were simultaneously injected with labelled and unlabelled lactate to obtain a lactate load similar to that of H animals. In the second normoxic group (N, control animals), animals were only injected with labelled lactate. During a 24 h recovery period, the incorporation of 14C and 3H into glycogen, lactate, glucose, amino acids, lipids and CO2 was measured. During recovery, glucose turnover rate was enhanced in H and depressed in NLL compared with N animals. However, when energy expenditure was taken into account, the changes were due only to a reduction of glucose turnover rate by lactate load. It was concluded that gluconeogenesis was not the main source of glyconeogenesis. Equivalent lactate loading in NLL and H animals resulted in an equivalent enhancement (fivefold) of lactate utilization in both groups when energy expenditure was taken into account. Lactate label incorporation appeared later in glycogen than in glucose, but remained high 24 h after the injection. Since glucose is mainly an extracellular metabolite, this observation may be consistent with the hypothesis of two distinct sites for glycogen restoration in hypogean crustaceans: a gluconeogenic organ (a liver equivalent) and a glyconeogenic organ (a muscle equivalent). The oxidative pathways of glucose and lactate were depressed in post-hypoxic N. virei and to a lesser extent in the NLL group. Since there is no evidence of marked protein utilization, it is postulated that, during recovery, repayment of the O2 debt relies on an increase in lipid utilization. During recovery from severe hypoxia or after a lactate load, the subterranean N. virei appeared to implement a strategy of lactate removal quite different from that observed in epigean crustaceans, favouring lactate-supported gluco- and glyconeogenesis and rapid glycogen replenishment instead of rapid lactate removal via oxidative pathways.

Reduction of I(Ca,L) and I(to1) density in hypertrophied right ventricular cells by simulated high altitude in adult rats.

The present paper describes the effect of a simulated hypobaric condition (at the altitude of 4500 m) on morphological characteristics and on some ionic currents in ventricular cells of adult rats. According to current data, chronic high-altitude exposure led to mild right ventricular hypertrophy. Increase in right ventricular weight appeared to be due wholly or partly to an enlargement of myocytes. The whole-cell patch-clamp technique was used and this confirmed, by cell capacitance measurement, that chronic high-altitude exposure induced an increase in the size of the right ventricular cells. Hypertrophied cells showed prolongation of action potential (AP). Four ionic currents, playing a role along with many others in the precise balance of inward and outward currents that control the duration of cardiac AP, were investigated. We report a significant decrease in the transient outward (I(to1)) and in the L-type calcium current (I(Ca,L)) densities while there was no significant difference in the delayed rectifier current (I(K)) or in the inward rectifier current (I(K1)) densities in hypertrophied right ventricular cells compared to control cells. At a given potential the decrease in I(to 1) density was relatively more important than the decrease in I(Ca,L) density. In both cell types, all the currents displayed the same voltage dependence. The inactivation kinetics of I(to 1) and I(Ca,L) or the steady-state activation and inactivation relationships were not significantly modified by chronic high-altitude exposure. We conclude that chronic high-altitude exposure induced true right ventricular myocyte hypertrophy and that the decrease in I(to 1) density might account for the lengthened action potential, or have a partial effect.

A case of life-threatening lactic acidosis after smoke inhalation - interference between beta-adrenergic agents and ethanol?

A 49-year-old male developed bronchospasm and severe lactic acidosis after exposition to fire smoke. The correction of lactic acidosis following beta-adrenergic agents withdrawal, and the transitory increase in lactate after salbutamol reintroduction are consistent with hypersensitivity to salbutamol. However, the plasma lactate concentration (32.6 mmol/l) that we observed 9.5 h after admission is far above those currently seen after administration of beta-adrenergic agents. We searched for causes able to potentiate the adverse effects of these drugs and we noticed that our patient had a high plasma ethanol level (2.4 g/l). Alcohol metabolism in the liver results in generation of high NADH/NAD+ ratios, thus reducing lactate liver clearance. This observation suggests that plasma lactate levels should be monitored closely in alcoholic patients treated with beta-mimetic agents.

Resistance of hepatic glycogen to depletion in obese Zucker rats.

Glycogen stores (liver and carcass) have been studied in lean and obese Zucker rats. The animals were submitted to one of three feeding conditions: ad libitum, a 48-h fast, or a 48-h fast and food ad libitum for 24 h, and to two environmental conditions, either thermoneutrality or an acute cold exposure (2 days at 4-7 degrees C). After a 2-day fast at 25 degrees C, the liver glycogen store was reduced by 45 times in the lean rats, while it was decreased by only 3 times in the obese rats. Under these conditions, the liver glycogen store was 45 times higher in the obese than in the lean rats. After 2 days in the cold, liver glycogen store was 4.4 times higher in obese rats than in lean rats. After a 2-day fast in the cold, the liver glycogen store in the obese rats was 30 times higher than in the lean rats. In comparison to fasting at thermoneutrality, fasting in the cold did not lead to a further reduction in hepatic glycogen in obese Zucker rats. The differences observed in the mobilization of the hepatic glycogen store between obese and lean rats have not been found in the mobilization of the carcass glycogen store. Drastic conditions, such as a 2-day fast in the cold, did not exhaust the glycogen store in obese Zucker rats. The present observations point out that obese Zucker rats cannot mobilize the entire hepatic glycogen store, as seen in lean control rats. The role of this abnormality in the high hyperlipogenesis that maintains the obese state is still to be evaluated.

Effects of the stress of sampling and of anaesthesia on the metabolic status of suckling rabbits.

The stress of anaesthesia and of sampling on the concentrations of blood metabolites and tissue glycogen content was studied in awake, anaesthetized and decapitated young rabbits 1-2 days old ("young") and 17-18 days old ("old"), 24 h after the last controlled suckling. Stress of sampling and anaesthesia was particularly evidenced by high blood lactate observed for the three protocols in young rabbits and to a lesser extent in old animals. Decapitation appeared as the less aggressive procedure for blood lactate assessment in "young" and "old" rabbits. In "young" rabbits, blood glucose was not significantly modified by the mode of blood sampling while in "old" rabbits blood glucose was significantly lower in awake than in anaesthetized animals. Muscle and liver glycogen content data were not significantly different between the three protocols in old and young rabbits. From a comparison of these results with those found in adult animals in various species, it appears that blood puncture in awake "young" and "old" rabbits is a suitable procedure for determining the majority of blood metabolites except lactate in "young" animals.

Depressed gluconeogenesis and ureogenesis in isolated hepatocytes after intermittent hypoxia in rats.

1. Rats were exposed to hypobaric hypoxia (equivalent altitude 4500 m), 2 x 2 hr per day, for 5 days. Isolated hepatocytes were prepared on day 6 after 18 hr of fast and also from control normoxic animals. The hepatocytes were incubated (120 min) with various substrates. 2. ATP contents were lower in hepatocytes from exposed as compared to control animals whether at the beginning (14%) or at the end (-6 to -33%) of incubation depending on the substrate. 3. Gluconeogenesis from all precursors (lactate, alanine, pyruvate, glutamine) was significantly reduced (40-50%) in exposed as compared to control animals. 4. Ureogenesis from alanine and from pyruvate + NH4Cl was also markedly depressed in exposed animals but no differences were noticed with glutamine or lactate + NH4Cl and alanine + NH4Cl. 5. Results are discussed in relation to known effects of acute and chronic hypoxia, interrelationship between gluconeogenesis and ureogenesis, taking into account the inhomogeneity of liver and the metabolic properties of periportal and perivenous hepatocytes.

Evolution of glycogen and blood metabolites after controlled suckling at two periods of lactation in young rabbits.

In natural conditions young rabbit nurses once a day and therefore ingests the whole of his daily caloric intake during a single meal. The present work investigates glucose homeostasis during perinatal period in young rabbit by assessing blood glucose and glycogen stores before and after one single meal. Ponderal data, glycogen and blood metabolites were determined in 1-4 day- and 17-21 day-old rabbits before suckling and at different times (1, 3, 6, 9, 24, 48, 72 h) after controlled suckling. In "young" and "old" rabbits hepatic glycogen stores were exhausted after 48 and 72 h of fast. Within the first hours following milk ingestion, muscle and carcass glycogen did not vary until 9 h in the "young" and until 24 h in the "old" without notable variation of glycemia. From 24 to 72 h young rabbits were in a fasting period with low hepatic glycogen and a decrease of muscle and carcass glycogen, but glycaemia decreased only slightly at 48 and 72 h in "young" and at 72 h in "old" As blood alanine was decreased, it appears that gluconeogenesis was effective and that alanine-glucose and Cori cycles were operating in these conditions.

Inhibitory effect of anaesthesia with 2-phenoxyethanol as compared to MS222 on glucose release in isolated hepatocytes from rainbow trout (Salmo gairdneri).

1. Glucose production by freshly isolated hepatocytes from rainbow trout was studied after anaesthesia of the animals with 2-phenoxy ethanol (2PE) or tricaine methanesulphonate (MS222). 2. At the end of the procedure, hepatic contents of glycogen, glucose, lactate, ATP, ADP, AMP, were not significantly different between the two treatments. 3. Glucose production was considerably lower for 2PE than for MS222 anaesthetized trouts. This discrepancy results probably from an inhibition of glycogenolysis, suggesting that 2PE anaesthetized animals were less stressed than MS222 anaesthetized ones.

Determination of glucose turnover in sea bass Dicentrarchus labrax. Comparative aspects of glucose utilization.

1. Parameters of in vivo glucose utilization by sea bass (132 +/- 6 g, mean +/- SEM) acclimated at 15 degrees C in sea-water were measured after single injection of labelled glucose. 2. Glucose turnover rate (RG; mumol . min-1 . kg-1) was found to be 0.55-065 (2-3H glucose) and 0.34 +/- 0.42 (U14C glucose). 3. Glucose transit time was 443-449 min, glucose mass 233-261 mumol . kg-1, and glucose recycling 37%. 4. Oxygen consumption (MO2) amounted to 94 +/- 6.2 mumol . min-1 . kg-1. 5. The comparison with other fish species, mammals and birds, taking into account body size, temperature, diet, exercise, in poikilotherms and homeotherms leads to the calculation of a glucose turnover index (RGI = RG x 6 x 100 x MO2(-1)). 6. Value of this, generally lower in ectotherm teleosts (2-9), than in endotherms: mammals, birds and thunidae (22-60), confirms the minor quantitative importance of glucose in the metabolism of most fish.

Comparison of glycogen stores in 3- and 7-month-old lean and obese Zucker rats under fed and fasted conditions.

Glycogen content (mg/g) and stores (mg) were determined in 3- and 7-month-old obese and lean Zucker rats, under fed and fasted (48 hr) conditions. Hepatic content was higher in fed obese than in lean rats (3 months: 90 vs 70; 7 months: 107 vs 74); it was exhausted after fasting in lean but decreased by 56% in obese rats. Muscle content in fed obese and lean animals did not differ; it decreased comparably after fasting. Myocardial content was higher in fed obese than lean rats (3 months: 7.2 vs 3.6; 7 months: 7.5 vs 6.3); it was enhanced with fasting (10.0 vs 7.5). Total glycogen stores were higher in obese than in lean animals (3 months: 2500 vs 1400; 7 months: 4000 vs 2000) because of the hepatic store. The discussion includes a comparison with available data, taking into account methodological aspects, lipid stores and the FFA/carbohydrate interrelationship.

Comparison of glycogen store in two strains of rat and guinea-pig under fed and fasted conditions.

Glycogen content in the liver, skeletal muscle and heart has been determined in Sprague-Dawley (SD) and Wistar (W) rats and in tricoloured (T) and albino Dunkin Hartley (DH) guinea-pigs. The 12-week-old animals were studied under non-fasted or control conditions (N) and after 48 hr of fast (F48). Hepatic glycogen was higher in DH guinea-pigs (95.6 +/- 3.8 mg g-1) than in W (77.2 +/- 5.3 mg g-1) and SD (80.2 +/- 2.3 mg g-1) rats under N conditions. Mean values for the two strains were slightly higher in guinea-pigs than in rats. After fasting, hepatic glycogen was almost exhausted in the two species but was higher in W (1.5 +/- 0.08 mg g-1) and T (1.5 +/- 0.2 mg g-1) than in SD and DH (0.6 +/- 0.1 mg g-1). The content of glycogen in the anterior muscles of the thigh was comparable in the two strains of rat and guinea-pig, but was twice as high in the guinea-pigs (DH:15.1 +/- 0.6; T: 16.4 +/- 0.7 mg g-1) as in the rats (SD: 8.1 +/- 0.2; W: 7.1 +/- 0.5 mg g-1) under N conditions. In F48 animals, muscular glycogen decreased by 41-46% (rats) and 38-39% (guinea-pigs). Hepatic and extra-liver glycogen stores were calculated and found higher in the guinea-pigs than in the rats. The total utilization during fasting was larger in the guinea-pigs (6140 mg/kg body wt) than in the rats (4500 mg/kg body wt).(ABSTRACT TRUNCATED AT 250 WORDS)

Substrates for cold thermogenesis in thyrotoxic dogs.

The influence of thyrotoxicosis on energy supply during cold exposure was studied in normal and chronically thyroxine (T4)-treated normothermic dogs exposed to neutral (Ta,N = +25 degrees C) or cold (Ta,C = -21 degrees C) ambient temperatures. At Ta,N, T4 treatment significantly increased VO2, glucose turnover, and plasma 3-hydroxybutyrate concentration. The percentage of glucose turnover derived from alanine also increased in spite of lower alanine release. In cold, T4 treatment did not significantly modify O2 consumption, glucose turnover, or plasma alanine concentration, but plasma hydroxybutyrate, alanine clearance, and alanine conversion into glucose were significantly increased compared with control. It is suggested that in cold the main effect of thyrotoxicosis on energy supply, in addition to a trend toward lipid mobilization, is an increase in hepatic alanine extraction and conversion into glucose in the presence of lower muscular alanine delivery.

[Metabolic myocardial modifications following surgical revascularization]. / Modifications métaboliques myocardiques après revascularisation chirurgicale.

The effects of aorto-coronary bypass surgery on myocardial lactate, free fatty acid and certain amino acid metabolism were studied in 30 coronary patients presenting with unstable, invalidating angina resistant to medical therapy. These patients had electrical signs of anterior wall ischemia without necrosis, significant proximal stenosis of the left anterior descending artery with good distal run-off, and underwent bypass surgery on this artery without signs of postoperative myocardial infarction. This study involved pre- and postoperative hemodynamic investigation with a Swan-Ganz catheter and a metabolic study of the coronary arteriovenous lactate (n = 30), free fatty acid, alanine and glutamate (n = 12) levels under basal conditions and after atrial pacing. These results were compared with those in 10 non-coronary control patients, operated for monovascular replacements. The increase of the pulmonary capillary pressure associated with a fall in systolic index at the 6th postoperative hour showed a reduction in left ventricular performance which tended to correct itself at the 24th hour. In the coronary patients, myocardial lactate production increased, alanine production increased and the uptake of free fatty acids fell during atrial pacing after surgery. These metabolic changes reflect the stimulation of anaerobic glycolysis secondary to myocardial ischemia which disappeared after surgery to compare with the control subjects. Therefore, effective myocardial revascularisation in patients with coronary artery disease is accompanied by the regression of the metabolic stigmata of myocardial ischemia.

Effect of cold ambient temperature on glucose and alanine turnover in dogs.

The metabolic effects of acute cold exposure were examined in dogs exposed to either +25 degrees C (TaN) or -21 degrees C (TaC). Simultaneous infusion of D-3-3H glucose and U-14C alanine was used to measure glucose (R Glu) and alanine carbon (R Ala) turnover rates. At the two ambient temperatures the animals remained normothermic and normoglycemic throughout the experiments. Cold exposure provoked a significant increase in VO2 (X 4.5), plasma 3-hydroxybutyrate concentration (X 1.8), R Glu (X 2.3) and alanine metabolic clearance (X 1.7), while plasma alanine concentration (X 0.4) and R Ala (X 0.6) were significantly decreased. At TaN and TaC, significant direct relationships were found between R (Ala) and plasma alanine concentration, the alanine fractional turnover rate being higher at TaC than at TaN. At the two ambient temperatures, inverse relationship was found between R (Ala) and plasma 3-hydroxybutyrate concentration. These experiments indicate that in spite of increased glucose needs, acute cold exposure is accompanied by reduced alanine release. They suggest that alanine plays only a minor role in cold-stimulated gluconeogenesis in dogs.

Effects of endogenous glucagon on glucose kinetics in shivering dogs.

Intravenous infusion of D-[3-3H]glucose at a constant rate was used to measure glucose production (rate of appearance, Ra) and utilization (rate of disappearance, Rd) in normal overnight-fasted dogs exposed to either neutral (TaN = +25 degrees C) or cold (TaC = -21 degrees C) ambient temperature. At TaC the metabolic rate was 4.1 times greater than at TaN and the dogs remained normothermic under both conditions. During control periods, cold exposure provoked a 2.2 times increase in hepatic Ra while plasma glucagon remained unaffected. Between two control periods somatostatin (1 microgram.kg-1.min-1 iv) and insulin (0.5 mU.kg-1.min-1 intraportal) were infused in such a manner that plasma insulin remained fairly constant at basal levels while glucagon dropped by 51% (TaN) and 66% (TaC), these percentages being not significantly different. This selective glucagon deficiency resulted in a 24% (TaN) and 30% (TaC) reduction in plasma glucose concentration, due to a 23% (TaN) and 25% (TaC) reduction in glucose production. There was a significant (r = 0.82, P less than 0.01) correlation between the control Ra and the reduction induced by the glucagon deficiency. At TaN and TaC, two significant parallel relationships were found between hepatic Ra and plasma glucagon concentration suggesting that glucagon has a modulatory effect on more fundamental mechanisms triggered by the cold-increased metabolic needs.

[Effect of physical training on the metabolic response of the isolated working heart during hypoxia (author's transl)]. / Effet de l'entraînement physique sur la réponse métabolique à l'hypoxie du coeur isolé de rat.

The increased tolerance to O2 deprivation of the myocardium after physical training was studied using the isolated working heart preparation and rats moderately trained by swimming. Glycolytic utilization of exogenous glucose and lactate production were determined under oxygenated conditions (Po2 # 500 Torr, 10 min), during severe hypoxia (P02 less than 50 Torr, 10 min) and during post-hypoxic perfusion (Po2 # 500 Torr, 15 min). The energetic state (CP, ATP, ADP, AMP) and glycogen store were determined at the end of the experimental procedure. The beneficial effect of training was evidenced by the restoration of aortic flow in the post-hypoxic period in hearts from trained animals (CE), whereas it did not return to the prehypoxic level in hearts from sedentary animals (CS). The increase in glycolytic utilization of exogenous glucose during hypoxia (x 2.5) was not very different in CE and CS, whereas lactate production was higher (+ 50%) and of longer duration in CE than in CS, This higher lactate production was the consequence of the larger glycogen store in CE than in CS. Moreover, glycogen resynthesis during the post-hypoxic period was higher in CE than in CS. Thus, a changed glycogen metabolism, and also higher CP and ATP contents in CE compared to CS, are examples of metabolic events implicated in the increased tolerance to O2 deprivation of the myocardium induced by physical training.

[Glucose metabolic clearance during acute cold exposure. Effects of insulin and glucagon (author's transl)]. / La clairance métabolique du glucose pendant l'exposition aiguë au froid. Effets de l'insuline et du glucagon.

The glucose metabolic clearance (CMG) was measured by using tritiated glucose in dogs either resting at neutral ambient temperature (TaN = + 25 degrees C) or shivering in the cold (TaC = 21 degrees C). Between two control periods, insulin and/or glucagon deficiencies were provoked by jugular somatostatin infusion without or with portal insulin (glucagon deficiency) or glucagon infusion (insulin deficiency). It was observed that: (1) In absence of hormonal deficiency, CMG was about twice as high at TaC as at TaN; (2) A simultaneous insulin and glucagon deficiency decreased CMG only at TaC; (3) Both at TaN and TaC, the CMG was either decreased or increased by insulin or glucagon deficiency respectively; (4) The magnitude (16-30%) of the hormonal-induced variations were small by comparison with the increase induced by the lowering of the ambient temperature.

[Possible contribution of amino-acids in myocardium response to hypoxia (author's transl)]. / Rôle éventuel des acides aminés dans la réponse du myocarde à l'hypoxie.

The purpose of the present report is to review current knowledge on amino-acid metabolism during hypoxia in vivo and in vivo, mainly in the myocardium. We have first considered biochemical events occurring in muscles during anoxia either in facultative anaerobic invertebrates or in aerobic vertebrates. In the invertebrate muscle, simultaneous utilization of carbohydrate and amino acids in anoxia leads to ATP formation and accumulation of CO2, alanine and succinate. In aerobic species, ATP production in anoxic conditions is mostly or totally derived from glycolysis, lactate being the end product. Recent studies from various authors have suggested that amino acid utilization may be present in aerobic species exposed to hypoxia and contribute to energy production under these conditions. Experiments using the isolated rat heart preparation have demonstrated the accumulation of alanine and succinate in addition to that of lactate during short period of hypoxia (Fig. 8). The relative importance of these biochemical events in term of energy production is discussed. It is also postulated that the accumulation of alanine and succinate in the myocardium during hypoxia may be involved in other physiological processes.