Short-term Effects of Diet and Activity Changes on Inflammation and Insulin Resistance.

The present study focused on rapid responses of inflammation markers and insulin resistance to dietary restriction and exercise in inactive patients. 13 obese women were included during a 5-day time frame during which decreases in food intake (-1 378±298 kcal) were associated with 2 exercise sessions (80 and 40 min). Circulating inflammatory biomarkers, insulin resistance index and muscle soreness were measured in fasted conditions. Fasting plasma concentrations of CRP and insulin resistance index decreased over the period (respectively, p=0.02 and p=0.01), concentrations of IL-6 and TNF-α appeared unchanged (p>0.05). Changes in IL-6 (enhanced) and TNF-α (reduced) concentrations following the prolonged exercise differed compared to days with 40 min exercise and days without exercise (p<0.05). Muscle soreness appeared higher after the 80 min than after the 40-min exercise (p=0.01), and were related with IL-6 and CRP concentration changes. A 5-day period combining exercise and diet reduced the insulin-resistance index and the CRP fasting concentrations. The 80-min exercise enhanced IL-6 and lowered TNF-α concentration changes while days without exercise unaffected these cytokines. These exercise effects on cytokines may have benefited to the insulin resistance index. The duration and number of the exercise sessions appeared sufficient for inactive subjects to initiate health benefits without inducing negative effects on inflammation and muscle soreness.

Onset of exercise and diet program in obese women: metabolic and anorexigenic responses related to weight loss and physical capacities.

Perturbations of energy balance induce compensatory processes that may alter expected weight loss. In obese patients, our aim was to investigate the relationships that occurred between fasting plasma concentrations of anorexigenic peptides and metabolic parameters, appetite, physical capacity, and weight loss in the 5 first days of a program associating exercise and caloric reduction. Thirteen obese women were monitored from day 1 to day 5 with 2 exercise sessions in day 2 and day 4. We measured, in a fasted state, changes in body weight, hunger ratings, and plasma concentrations of fatty acids, triglycerides, leptin, insulin, amylin, peptide YY, and insulin-resistance index. Physical performance was assessed by a 6-min walking test. The program resulted in significantly reduced body weight (0.75±0.4 kg; p=0.001), of plasma concentrations of triglycerides, insulin, amylin, peptide YY, and the insulin-resistance index, and also increased fatty acids (p<0.05). Hunger ratings were increased (p<0.05). Program-induced changes in fatty acids, leptin, and insulin concentrations were related to physical performance (r(2)=0.45, 0.59, and 0.52; p<0.05, respectively) and to weight loss (r(2)=0.65, 0.57, 0.55; p<0.05, respectively). Five days of diet and exercise induced weight loss, improved lipid profile, and decreased insulin resistance while hunger ratings increased. Subjects with higher physical capacity lost more weight, presented higher increases in fatty acids and lower changes of leptin and insulin concentrations suggesting a better metabolic flexibility. To reduce the compensatory responses that can occur with energy imbalances, our study supports to account for individual activity level before prescribing weight-loss program associating diet and exercise.

Summer influenza outbreak in a home for the elderly: application of preventive measures.

Influenza outbreaks occasionally occur in nursing homes (NHs) despite vaccination, but occurrence during summer is a rare event. We describe an influenza outbreak during a heatwave in 2005, and discuss the usefulness of rapid diagnosis in facilitating early intervention as well as appropriate infection control measures. An outbreak was observed in a single NH with 81 residents (mean age 88 years) and 48 healthcare workers (HCWs) and lasted seven days. Fever, cough and wheezing were reported as the main symptoms in 32 affected residents (39.5%) and 6 (12.5%) HCWs. Influenza was suspected and provisionally confirmed by a rapid diagnostic test performed on specimens from four patients. The outbreak was further confirmed by culture and reverse transcriptase-polymerase chain reaction in seven out of 10 residents. The strain was similar to the winter epidemic strain of the 2004-2005 season: H3N2A/New York/55/2004. As soon as the outbreak was confirmed, a crisis management team was set up with representatives of the local health authority and NH staff. A package of measures was implemented to control the outbreak, including patient isolation and the wearing of surgical masks by all residents and staff. A therapeutic course of oseltamivir was prescibed to 19/32 symptomatic patients and to 5/6 HCWs, and 47 residents and 42 remaining HCWs received a prophylactic post-exposure regimen. The outbreak ended within 48 h. Case fatality rate was 15.6% among residents. Pre-outbreak influenza vaccine coverage among the residents was 93.5% and 41.7% in HCWs. The rapid diagnostic test enabled prompt action to be taken, which facilitated infection control measures.

Splanchnic sequestration of amino acids in aged rats: in vivo and ex vivo experiments using a model of isolated perfused liver.

Splanchnic sequestration of amino acids (SSAA) is a process observed during aging that leads to decreased peripheral amino acid (AA) availability. The mechanisms underlying SSAA remain unknown. The aim of the present study was to determine whether a high-protein diet could increase nitrogen retention in aged rats by saturating SSAA and whether SSAA could be explained by dysregulation of hepatic nitrogen metabolism. Adult and aged male Sprague-Dawley rats were housed in individual metabolic cages and fed a normal-protein (17% protein) or high-protein diet (27%) for 2 wk. Nitrogen balance (NB) was calculated daily. On day 14, livers were isolated and perfused for 90 min to study AA and urea fluxes. NB was lower in aged rats fed a normal-protein diet than in adults, but a high-protein diet restored NB to adult levels. Isolated perfused livers from aged rats showed decreased urea production and arginine uptake, together with a release of alanine (vs. uptake in adult rats) and a hepatic accumulation of alanine. The in vivo data suggest that SSAA is a saturable process that responds to an increase in dietary protein content. The hepatic metabolism of AA in aged rats is greatly modified, and urea production decreases. This result refutes the hypothesis that SSAA is associated with an increase in AA disposal via urea production.

The equivocal metabolic response to endotoxaemia in type 2 diabetic and obese ZDF rats.

AIMS/HYPOTHESIS: The metabolic and endocrine disturbances associated with obesity and type 2 diabetes may impair the normal metabolic response to injury. Our objective was to investigate amino acid metabolism in endotoxaemic type 2 diabetic obese rats. MATERIALS AND METHODS: A metabolic study was performed over 4 days using male Zucker diabetic fatty (ZDF) rats (fa/fa) and lean littermates (fa/+) divided into three groups: ad libitum-fed groups which underwent no treatment, lipopolysaccharide (LPS)-treated groups receiving E. coli LPS by i.p. injection, and pair-fed groups to the respective LPS groups. We evaluated the effect of endotoxaemia on body weight, food intake and tissue weights. Nitrogen loss and muscular proteolysis were measured daily by determination of urinary 3-methylhistidine (3-MH) excretion. Plasma, intestine and muscle amino acid levels were measured. RESULTS: The data showed that ad libitum-fed ZDF rats had lower plasma arginine and glutamine levels than ad libitum-fed control rats. Compared with control rats, the LPS-treated ZDF rats presented lower thymic involution, a lower 3-MH:creatinine ratio and higher cumulative nitrogen balance. CONCLUSIONS/INTERPRETATION: Against our working hypothesis, ZDF rats did not show an impaired metabolic response, and even appeared to be less sensitive to the stress.

Cytotoxic response of sinusoidal endothelial cells to polymorphonuclear leukocytes and its potential implication in hypoxia-reoxygenation injury.

AIMS: Interactions between polymorphonuclear leukocytes (PMN) and sinusoidal endothelial cells (SEC) may contribute to ischemia-reperfusion injury. The aim of the study was to determine the influence of PMN hypoxia-reoxygenation and degranulation, on SEC toxic response. METHODS: PMNs collected from rat pleural cavity underwent hypoxia- reoxygenation or N-formyl-methionyl-leucyl-phenylalanine (fMLP) degranulation treatment, and were then separated from their conditioned medium. Rat SECs were incubated either with PMNs in coculture or with their conditioned medium, for 210 min. Oxidative metabolism in PMNs was measured by chemiluminescence. LDH release and elastase activity were measured in SEC supernatants. RESULTS: PMN-conditioned medium induced an increase in LDH release in SECs. Hypoxia-reoxygenation of PMNs induced an increase in their chemiluminescent response without increasing the cytotoxic effect of their conditioned medium. By contrast, the cytotoxic effect of conditioned medium was increased following PMN treatment with fMLP. In the latter case, cytotoxicity was combined with a rise in the elastase activity released in the supernatants, but was not reduced by inhibitors of elastase or of other proteases. CONCLUSIONS: The results indicate that toxic products are released, at least in part through degranulation, by PMNs, and induce cytotoxicity in SECs. This mechanism may contribute to SEC injury during hypoxia-reoxygenation.

Evaluation of a newly available biochemical analyzer: the Olympus AU 600.

The performance of the Olympus AU 600, a newly available open multiparametric analyzer, available for routine biochemical analysis of biological samples, was evaluated. The analytical and technical performance of the apparatus and the quality of the Olympus reagents were both examined in a single site study. Electrolyte concentrations were determined with patented ion-selective electrodes; substrate concentrations and enzyme activities were determined by spectrophotometric measurement after coloured reaction or UV detection-based-reactions. The protocol of the evaluation and the acceptability criteria were those recommended by the French Society for Clinical Biology. For the parameters studied, the upper limits of linearity were equal to or higher than those claimed by the manufacturer. The CV values for within-run and between-run precision were lower than the target values with few exceptions. The comparison study gave satisfactory results for most of the parameters. Only expected interferences occurred. In summary, the results obtained for the 25 parameters studied and the characteristics of the apparatus were satisfactory. The analyzer is rapid (800 to 1200 tests per hour) and easy to use. In addition, the analyzer complies with good analytical practice and its flexibility enables users to plan work according to local laboratory constraints.

Hepatoprotective effect of endogenous nitric oxide during ischemia-reperfusion in the rat.

The aim of this study was to evaluate the protective or deleterious effects of endogenous nitric oxide (NO) on liver cells during hepatic ischemia-reperfusion (IR) in the rat. Injury to hepatocytes and endothelial cells was evaluated by determining cytolysis-marker activity in plasma (alanine transaminase [ALT]; aspartate transaminase [AST]) and plasma hyaluronic acid (HA) concentration. Clamping the hepatic pedicle for 45 minutes caused a significant increase in plasma AST and ALT activity after 30 minutes of reperfusion, which reached a maximum (+270% and +740%, respectively) after 6 hours of reperfusion. Plasma HA concentration was significantly higher (+130%) only after 6 hours of reperfusion. Administration of a nonselective NO synthase (NOS) inhibitor, Nomega-nitro-L-arginine (L-NNA; 10 mg/kg iv), 30 minutes before IR, caused marked aggravation of postischemic liver injury, as shown by plasma ALT and AST activity and HA concentration. This deleterious effect was partially prevented by the simultaneous injection of L-arginine, the endogenous NO precursor (100 mg/kg iv). Interestingly, L-arginine alone limited postischemic damage (AST, -25%; ALT, -45%; HA, -21% vs. untreated IR rats at 6 hours reperfusion). Pretreatment with the Guanosine 3':5'-cyclic monophosphate-independent vasodilator, prazosin, partially reversed L-NNA effects, but it did not protect untreated IR animals. Pretreatment with aminoguanidine, a selective inhibitor of inducible NOS, did not aggravate hepatic IR injury. Thus, endogenous NO, probably produced by an early and transient activation of a constitutive NOS, protects both hepatocytes and endothelial cells against liver ischemia-reperfusion injury, and this effect is not entirely a result of vasorelaxation.

Direct cytotoxicity of hypoxia-reoxygenation towards sinusoidal endothelial cells in the rat.

AIMS/BACKGROUND: Sinusoidal endothelial cells are the primary target of ischemia-reperfusion injury following liver preservation. The present study was undertaken to examine the susceptibility of sinusoidal endothelial cells to hypoxia-reoxygenation and the potential role of oxygen free radicals in the induction of cell injury. METHODS: Sinusoidal endothelial cells were isolated from rat liver. After 2 3 days of primary culture, the cells were exposed to hypoxia (N2/CO2 95/5) for 120 min and reoxygenation (O2/CO2 95/5) for 90 min. Control cells were exposed to hypoxia alone, to 95% O2 alone or were maintained under normoxic conditions. Human umbilical vein endothelial cells were used as a model of vascular endothelial cells and submitted to the same protocol. Cell viability and lipid peroxidation were assessed by LDH leakage and malondialdehyde production, respectively. In order to test the potential role of xanthine oxidase and mitochondrial dysfunction in cell injury, the cells were treated with allopurinol and potassium cyanide (KCN) respectively. RESULTS: The different gaseous treatments did not affect LDH leakage in human umbilical vein endothelial cells. In sinusoidal endothelial cells, the sequential hypoxia-reoxygenation caused a significant increase in LDH release, malondialdehyde production and xanthine oxidase activity while hypoxia alone had no effect except on xanthine oxidase activity. Allopurinol inhibited xanthine oxidase without preventing cell injury or lipid peroxidation in this latter cell type. CONCLUSIONS: The results suggest that sinusoidal endothelial cells, as opposed to vascular endothelial cells, are susceptible to a direct cytotoxic effect of hypoxia-reoxygenation. This effect occurs in combination with an increase in xanthine oxidase activity and lipid peroxidation, although cell injury is mediated at least in part by mechanisms independent of xanthine oxidase such as mitochondrial dysfunction.

Bile acid inhibition of interferon activity in human lymphocytes: no evidence of oxidative stress.

Cholestasis and bile acids are two factors involved in resistance to interferon therapy in patients with chronic hepatitis C. As bile acids inhibit the biological activity of this cytokine in vitro and are capable of generating oxidative stress in hepatocytes, we investigated the potential involvement of such a mechanism in human lymphocytes. Thus, we evaluated (a) the effects of bile acids (0-200 mumol L-1) on lymphocyte reduced glutathione content and malondialdehyde production and (b) the ability of antioxidants to prevent the inhibitory effect of chenodeoxycholic acid on interferon-induced lymphocyte 2',5'-oligoadenylate synthetase activity, an index of the biological activity of interferon. We found that treatment of lymphocytes with bile acids for 24 h did not induce malondialdehyde release or significantly modify cellular reduced glutathione content. Synthetic precursors of glutathione (N-acetylcysteine and S-adenosylmethionine) and antioxidants (superoxide dismutase and catalase) had no preventive influence on the inhibitory effect of chenodeoxycholic acid on interferon-induced 2',5'-oligoadenylate synthetase activity. These negative results do not provide evidence for the use of glutathione precursors in cholestatic conditions associated with viral diseases.

Treatment of chronic myelogenous leukemia in blast crisis and in accelerated phase with high- or intermediate-dose cytosine arabinoside and amsacrine.

Twenty-two patients (mean age 41 years) in blast crisis or accelerated phase (AP) of chronic myelogenous leukemia (CML) were treated with cytosine arabinoside (Ara-C) 500 mg/m2 [intermediate dose] or 1000 mg/m2 [high dose] twice a day for 6 days and amsacrine (AMSA) 120 mg/m2 for 3 days. Twenty-one cases were of myeloid type and one was a lymphoid BC. The mean duration of aplasia (neutrophils < 0.5 x 10(9)/l) was 21.5 days. Four patients (18%) died of infection during aplasia and minor toxicities were noted for the remainders. Nine patients (41%) achieved a complete remission (CR) and 4 (18%) a partial response. Various additional therapies were proposed after induction treatment including allogeneic bone marrow transplantation (2 patients), Ara-C and AMSA maintenance or other regimens with or without alpha-interferon (9 patients). Median survival for the entire cohort was 20 weeks (wks), significantly superior for complete responders (37 wks) than for others (7 wks) (p = 0.008). In this study, age, sex, initial platelet or basophil counts, interval between diagnosis of CML and blast crisis were not predictive of response. Although inducing a high CR rate and associated with acceptable toxicity, this regimen did not improve the survival of patients with BC or CML, strengthening the need for alternate approaches to be defined.

[Effects of isoflurane and halothane on the auditory and somatosensory evoked potentials]. / Effets de l'isoflurane et de l'halothane sur les potentiels évoqués auditifs et somesthésiques.

The effects of isoflurane and halothane anaesthesia on brainstem auditory (BEAR) and somatosensory evoked potentials (SEP) were recorded in 15 patients; eight received isoflurane and seven halothane. Atropine alone was given as premedication. After induction of anaesthesia with thiopentone, it was maintained with 50% nitrous oxide in oxygen. Ventilation was controlled. Isoflurane and halothane concentrations were gradually increased to 3%. Recordings were made at 1%, 2.5% and 3%. There were statistically significant differences in the latencies of SEP and BEAR with increasing concentrations of anaesthetic. The BEAR waves significantly affected were wave V and the latency between peaks I to V (p less than 0.001); for the SEP, it was wave N20. SEP central conduction time was prolonged with both anaesthetics (p less than 0.001). The effects of isoflurane and halothane were similar. These results could not be explained by changes in central body temperature or end-tidal carbon dioxide concentration. The study showed a dose-related direct effect of both anaesthetic agents on the brainstem auditory and somatosensory evoked responses. It may be that the measurement of changes in evoked potentials could be a useful indicator of anaesthetic depth.

[Enteral nutrition by tube in burn patients]. / Alimentation entérale par sonde chez le brulé.

The authors report a year's experience off artificial feeding (A.F.) in the Regional Burns Centre of Marseille. 28 patients have benefited from an A.F. of longer than 10 days. It consisted of four cases of parenteral feeding, six cases of enteric feeding and eighteen cases of combined parenteral and enteric feeding. The efficiency of the techniques of A.F. is demonstrated by the results: a weight loss greater than 10% was observed in only three patients. However, the phenomena of digestive intolerance in this type of patient is a significant limiting factor in tubal feeding.

[The heterogeneity of micropolycystic ovary syndrome. 77 cases (author's transl)]. / L'hétérogénéité du syndrome des ovaires micro-poly-kystiques. Etude de 77 observations.

Seventy seven cases of micropolycystic ovaries were reviewed. All of the patients underwent either coelioscopy or wedge resection of the ovaries. It was thus possible to classify the patients into two groups on the basis of the size of the ovaries (MPCO-A, large ovaries, more than twice the normal size; MPCO-B, ovaries only slightly increased in size or normal). There were differences from a clinical, laboratory and therapeutic standpoint. In MPCO-A, spaniomenorrhea predominated, clinical hyperandrogenism was often absent and 17 ketosteroids lower. Response to hypothalamic gonadotrophic hormone liberation factor was explosive in luteotrophic hormone, but at 120 minutes levels were lower in MPCO-A than in MPCO-B. Wedge resection failed completely in 23% of cases of MPCO-A and in 66% of cases of MPCO-B. This study confirmed current concepts of the heterogeneity of MPCO syndrome.

[Traumatic intoxication by an anticholinesterase agent]. / Intoxication "traumatique" par un anticholinestérasique.

An unusual observation is reported concerning intoxication by an anticholinesterasic. In this case a traumatic blow was caused by an industrial liquid projected under high pressure and resulted in a true parenteral injection. This product, presumed not to be toxic, lead to the delayed appearance of a massive and eventually fatal intoxication. The problemes of prevention, diagnosis and treatment of this type of intoxication are commented on.

[The effects of age and sex on the acute toxicity of two barbiturate anesthetics in rats]. / Influence de l'âge et du sexe sur la toxicité aiguë de deux anesthésiques barbituriques chez le rat.

The study of the acute toxicity of two barbiturics anaesthetics (pentobarbital and thiopental) shows the newborn period a higher susceptibility of the young rat, probably due to an immaturity of biotransformations enzymatic systems or to an increased blood-brain-barrier permeability.

[Blood coagulation during prolonged postoperative parenteral feeding containing lipids]. / Evolution de la coagulation sanguine au cours des alimentations parentérales post-opératoires prolongées comportant des lipides.

Blood coagulation was studied in two groups of fifteen patients of the same type during parenteral nutrition lasting for more then ten days and given during the postoperative period. The first batch of patients, taken as a control group, received parenteral nutrition with carbohydrates and proteins, whilst the second group received lipids in addition. Study of blood coagulation, carried out every three days, involved : thromboelastogen on whole blood and plasma, platelet count, platelet adhesiveness and the estimation of factors II, V, VII and X, fibrinogen, plasminogen and fibrinogen break-down products. In the patients not receiving lipids, the normal alterations seen during the postoperative period occurred : normalisation in plasminogen levels and in F.B.P., and an increase in the number of platelets and in fibrinogen level. The presence of lipids in the nutritional fluids resulted in changes in the same direction, but the increase in platelet count was slighter and fibrinogen level, after a slight increase, returned to initial values on the 20th day of parenteral nutrition. Fibrinogen was the only factor which showed any significant difference between the two groups.

[Influence of age and sex on the acute toxicity of two steroid anesthetics in rats]. / Influence de l'âge at du sexe sur la toxicité aiguë de deux anesthésiques stéroïdiens chez le rat.

During the newborn period, there is a hight increase of the acute toxicity of two steroid anaesthetics (Hydroxydione, Althesin) given by intraperitoneal route on the rat as also an influence of hormonal conditions.