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Increased VLDL-TAG turnover during and after acute moderate-intensity exercise.

PURPOSE AND METHODS: Breakdown rates of very low density lipoprotein triacylglycerols (VLDL-TAG) were quantified before (3 h), during (45 min), and after (3 h) moderate physical exercise at 40% VO2 max in young sedentary subjects (four male and four female, age 29.8 +/-1.6 yr, BMI 24.1 +/- 0.9 kg x m, VO2max 37.0 +/- 1.7 mL x kg x min), using boluses of H5-glycerol (100 mu mol x kg) and H2-palmitate (6.6 mu mol x kg). The catabolic rates of VLDL-TAG were calculated from the decay in the isotopic enrichment using a single-pool model. The results were compared with those obtained during 6 h of rest in five of the same volunteers. RESULTS: VLDL-TAG concentration remained constant throughout the study with exercise (P = NS). The fractional catabolic rate was nearly doubled from rest to exercise (P < 0.05 vs rest) and increased to an even greater extent during the early phase of recovery (P < 0.001 vs rest). During the late recovery phase, the value returned to the preexercise value (P = NS vs rest). The values for the absolute catabolic rate (kabs) followed the same trend. CONCLUSION: VLDL-TAG turnover was increased during exercise and during the early phase of recovery.

Adult↗

Effect of pilsicainide on atrial electrophysiologic properties in the canine rapid atrial stimulation model.

The heterogeneous process of atrial electrical remodeling (AER) in the canine rapid atrial stimulation model has been previously reported although it has been reported that a sodium channel blocker might suppress the shortening of the atrial effective refractory period (AERP), its effect on long-term electrical remodeling is unknown. In the present study, the effect of pilsicainide on AER was evaluated. The right atrial appendage (RAA) was paced at 400 beats/min for 2 weeks. In the RAA, Bachmann's bundle (BB), the right atrium near the inferior vena cava (IVC) and in the left atrium (LA), AERP, AERP dispersion (AERPd) and the inducibility of atrial fibrillation (AF) were evaluated at several time points of the pacing phase and the recovery phase (1 week). The same protocol was performed during the administration of pilsicainide (4.5 mg/kg per day) and the parameters were compared with the controls. In the control dogs, the AERP was significantly shortened by rapid pacing at all atrial sites studied and the AERP shortening (DeltaAERP) was larger at the RAA and LA sites (p<0.03). However, pilsicainide decreased these DeltaAERPs at all 4 atrial sites. AERPd was increased during the pacing phase whereas it was decreased during the recovery phase in the control dogs. In contrast, this pacing-induced AERPd was attenuated by the administration of pilsicainide. The AF inducibility was highest at the LA site in both groups, and the inducibility was lower in the pilsicainide group than the control group at all atrial sites. During the rapid pacing phase, the ventricular heart rate was significantly lower in the pilsicainide group than the control because of intra-atrial conduction block. In a canine rapid right atrial stimulation model, pilsicainide suppressed the shortening of the AERP at all atrial sites, possibly through the improvement of the hemodynamics as well as the action of the Na - Ca exchanger.

Animals↗

Serum regulated upon activation, normal T cell expressed and presumably secreted concentrations and eosinophils in respiratory syncytial virus infection.

BACKGROUND: The aim of this study was to characterize respiratory syncytial virus (RSV) infection. To do this, the authors evaluated eosinophil counts and chemokines including regulated upon activation, normal T cell expressed and presumably secreted (RANTES) in children with RSV, adenoviral, and influenza virus infections. METHODS: The authors enrolled 80 patients who had been diagnosed with acute viral respiratory infection caused by RSV, adenoviral, or influenza viruses. In total, 35 patients (Group A) had RSV infection, 18 (Group B) had adenoviral infection, and 27 (Group C) had influenza virus infection. The authors evaluated clinical manifestations, white blood cell and eosinophil counts, and serum chemokines including RANTES concentrations in the acute and recovery phases in each group. RESULTS: In recovery phase, eosinophil counts were higher in Group A than Groups B and C. In Group A, eosinophil counts were higher in recovery phase than in the acute phase. In Group A, serum RANTES concentration was significantly higher in the recovery phase than in the acute phase (132+/-76 pg/mL vs 52+/-25 pg/mL, P<0.05). CONCLUSION: The findings suggest that high values of RANTES in children with RSV infection may be associated with the presence of eosinophils and be an important mediator of inflammatory response.

Adenovirus Infections, Human↗

Verapamil suppresses the inhomogeneity of electrical remodeling in a canine long-term rapid atrial stimulation model.

Verapamil is known to suppress shortening of the atrial effective refractory period (AERP) during relatively short-term atrial pacing, although the effect of a long-term stimulation model is unclear. The effect of verapamil on electrical remodeling was evaluated in a canine rapid atrial stimulation model. The right atrial appendage (RAA) was continuously paced (400 beats/min) for 2 weeks. Four pairs of electrodes were sutured at four atrial sites; the RAA, right atrium close to the inferior vena cava, Bachmann's bundle, and LA. AERP, AERP dispersion (AERPd), conduction time, and inducibility of AF were evaluated during the pacing phase and the recovery phase. The same protocol was performed under the administration of verapamil. In five control dogs, the AERP shortening was inhomogeneous and the shortening of the AERP was most prominent in the LA. AERPd increased during the rapid pacing phase by 5 +/- 2 ms, but recovered quickly in the recovery phase. The max AERPd was 46 +/- 4 ms in the control group and was larger than that in the verapamil group (31 +/- 3 ms, P = 0.001). At the LA site, the shortening of the AERP was decreased by verapamil administration (-19 +/- 3 vs -5 +/- 2 ms, P = 0.04). However, the AF inducibility was not significantly different between the two groups. The effect of verapamil on electrical remodeling was inhomogeneous, depending on the anatomic portion. As a result, AERPd widening during the rapid pacing phase was suppressed by verapamil, while the AF inducibility was unchanged.

Analysis of Variance↗

Effect of Eimeria acervulina infection on nutrient retention with special reference to fat malabsorption in chickens.

Nutritional balance studies were conducted to determine the effect of Eimeria acervulina infection on the retention of nutrients and the efficiency of utilization of protein and energy in the diet during the course of intestinal coccidiosis in chickens. Both light and electronmicroscopic studies were conducted to elucidate the pathogenesis of fat malabsorption in the infected chickens. The infection with E. acervulina during the acute phase of the disease (day 4 to day 8 postinfection) caused a reduction (P smaller than 0.01) in the retention of percent protein, percent ether extract and percent gross energy of the diet with a concomitant increase (P smaller than 0.01) in the concentration of ether extract and gross energy of the excreta. The metabolizable energy value of the diet was also depressed during this phase. During the recovery phase of the disease (day 9 to day 13 postinfection) infected chickens voided excreta containing a slightly greater concentration of ether extract when compared to the controls but differences in the retention of percent protein and percent gross energy were no longer observed. An increased retention of percent phosphorus also occured during the recovery phase. Studies involving the carcass composition revealed that the efficiency of utilization of protein and metabolizable energy of the diet for tissue deposition was reduced (P smaller than 0.05) during day 0 to day 8 postinfection but only the efficiency of metabolizable energy utilization was found to be depressed (P smaller than 0.05) when data for day 0 to day 14 postinfection were analyzed. Both light and electronmicroscopic studies of the duodenal villi of infected chickens during day 5 to day 6 postinfection revealed accumulation of large globules of fat in the villus epithelial cells parasitized by the gammonts of E. acervulina indicating a possible blackade of "fat exit" from these cells.

Animal Feed↗

Aspects of the neuroendocrine control of somatotropic function in calorically restricted dogs and patients with eating disorders: studies with cholinergic drugs.

A series of studies was devised in both an experimental model of food deprivation, i.e., beagle dogs undergoing a progressive reduction of calorie intake and adolescent females with anorexia nervosa (AN) in the acute and recovery phase, and in patients with atypical eating disorders. The studies were aimed at ascertaining whether the alleged function of the hypothalamic system inhibitory to growth hormone (GH) secretion, i.e., the somatostatinergic, may account for at least some of the abnormalities of GH secretion present in AN patients (e.g., elevated basal GH levels, paradoxical GH rise after glucose or thyrotropin releasing hormone, etc). Caloric restricted dogs or patients with eating disorders were given an intravenous injection of the physiologic GH-releasing peptide GHRH alone or preceded by pirenzepine, a muscarinic cholinergic antagonist reportedly capable of eliciting hypothalamic release of somatostatin (SS), or pyridostigmine, a muscarinic cholinergic agonist which, conversely, would restrain hypothalamic release of SS. In addition, dogs were challenged with acute administration of glucose or thyrotropin-releasing hormone, compounds also thought to act via somatostatinergic influences. Data obtained in dogs under caloric restriction or in AN patients in the acute phase of the disease with drugs affecting cholinergic transmission suggest that the latter is increased in both conditions (only partial suppression of the GHRH-induced GH rise with pirenzepine, failure of pyridostigmine to further enhance the GH response to GHRH). Instead, in the same AN patients in the acute phase tested during recovery, in AN patients during the recovery phase, and in patients with atypical eating disorders, pirenzepine completely suppressed the GH response to GHRH, as it did in controls. Finally, data obtained on basal and GHRH-stimulated GH release in dogs given glucose or thyrotropin-releasing hormone and in AN patients given arginine, another compound thought to act via inhibition of somatostatinergic influences, do not support the view that somatostatinergic function is impaired in states of food deprivation.

Adolescent↗

Vascular viscoelasticity of perfused rat hindquarters.

To determine viscoelastic features of the rat hindquarters vasculature, we measured pressure-volume curves. Male Wistar rats were transected at the lumbar level, and the perfused hindquarters were oxygenated with a hollow fiber artificial lung. The blood volume was measured by counting 51Cr-labeled red cells led to a gamma counter through an extracorporeal circuit at a constant rate. With continuous monitoring of the venous pressure and circulating blood volume, saline was infused into the circuit from a venous branch for 5 min [1.2 +/- 0.3% (SD) of tissue weight] followed by a 10-min recovery phase. In the recovery phase, the venous pressure promptly declined to the preinfusion level, whereas the circulating blood volume decreased more slowly. This implied vascular stress relaxation of the hindquarters. Maxwell's viscoelastic model, consisting of a spring component and a viscous component, was applied to analyze the venous pressure-volume diagram. With a curve-fitting method, the calculated vascular compliance and relaxation time (a time constant of stress relaxation) were 1.31 +/- 0.14 ml.mmHg-1.kg-1 and 15.7 +/- 4.0 min (means +/- SE), respectively. The value of compliance of the hindquarters was smaller than those of visceral organs reported. In addition, the value for relaxation time suggests that the viscous response of the vasculature simultaneously overlaps change in blood volume due to extravascular fluid shift during the postinfusion period.

Animals↗

Pressure response to quick volume changes in tetanized isolated ferret hearts.

Observed pressure responses to quick volume changes in the isolated tetanized heart of ferrets were compared with previously reported tension responses to quick length changes in isolated cardiac muscle. Hearts were isolated from ferrets, perfused with ryanodine solution, and stimulated rapidly (50 ms between stimulations) to produce repeated 4-s intervals of tetanus. During each tetanus interval, volume increments of different amplitudes were rapidly removed and then reinfused into the left ventricular chamber. The pressure responses to these volume changes were evaluated for differences between withdrawals and infusions and for dependence on the amplitude of the volume change. It was found for both withdrawal and infusion that the response could be divided into three phases: 1) an immediate phase coincident with volume change, 2) a fast-recovery phase, and 3) a slow-recovery phase. The amplitude of the immediate phase was linearly dependent on the volume change so that a single regression line fit all the data (withdrawal and infusion). The fast recovery phase was 2.5 times faster for infusion than for withdrawal and generated a rebound effect with the pressure going below the initial pressure in the response to infusion. The pressure never went above the initial pressure in the response to withdrawal. The slow-recovery phases in infusion and withdrawal did not differ. These responses in the isolated heart bear striking similarities to tension responses to quick length changes in isolated constantly activated cardiac muscle. We concluded that muscle fiber dynamics were being faithfully transformed to left ventricular (LV) chamber dynamics without appreciable distortion because of the many intervening factors between the wall muscle fiber and the LV chamber.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Dynamic change of cells expressing MMP-2 mRNA and MT1-MMP mRNA in the recovery from liver fibrosis in the rat.

BACKGROUND/AIMS: The aim of this study was to investigate whether both matrix metalloproteinase-2 (MMP-2) and membrane type 1 MMP (MT1-MMP) participate in the spontaneous resolution of liver fibrosis. METHODS: Transcription of both genes was examined by reverse transcription-polymerase chain reaction (RT-PCR) and in situ hybridization (ISH). Gelatinase activity was investigated by zymography. RESULTS: Gene expression by RT-PCR showed that both genes increased in the process of liver fibrosis, then decreased gradually in the recovery phase. ISH revealed that distribution of positive cells changed quickly in the recovery phase. Positive cells were widely seen in the liver, mainly around fibrous septa, in the aggressive phase, but were exclusively observed at the interface between the resolving fibrous band and the parenchyma, then were diffusely located in the lobules in the recovery phase. Main cells expressing both mRNAs seemed to be stellate cells for their morphology, though they did not express characteristic cell markers. Some hepatocytes and Kupffer cells expressed both mRNAs in the recovery phase. Gelatinase activity of MMP-2 increased in the recovery phase of 8-week-treated rat liver by gelatin zymography. CONCLUSIONS: The results of present study suggest that both enzymes participate in the destruction of extracellular matrix in coordination with MMP-13.

Animals↗

2',5'-Oligoadenylate synthetase activity and T cell subset in the cerebrospinal fluid and peripheral blood of aseptic meningitis.

2',5'-oligoadenylate synthetase activity, which is assumed to be induced by interferon, is reported to be one of the useful markers reflecting interferon activity. The enzyme activity of patients with aseptic meningitis and febrile convulsion were compared in order to evaluate interferon activity as one of the local immuno-defense mechanisms of aseptic meningitis. The surface antigen of mononuclear cells in cerebrospinal fluid and peripheral blood of some patients with aseptic meningitis was also measured. The enzyme activity of patients with aseptic meningitis was 191.4 pmol/dL in the cerebrospinal fluid and 395.8 pmol/dL in the serum during the acute phase, while that of patients with febrile convulsion was 45.2 pmol/dL in the cerebrospinal fluid and 326.0 pmol/dL in the serum. The enzyme activity of the former patients significantly decreased during the recovery phase in both the cerebrospinal fluid and serum. CD3 positive cells in the peripheral blood were 56.3% of the total mononuclear cells during the acute phase and 65.2% during the recovery phase, whereas in the cerebrospinal fluid mononuclear cells, they were 87.1 and 85.5%, respectively. During the acute phase, CD4 positive cells were the predominant T lymphocyte subset in the cerebrospinal fluid cells, while CD8 positive cells were predominant during the recovery phase. The relative proportions of CD4 positive and CD8 positive cells during the acute and recovery phase in the cerebrospinal fluid mononuclear cells were quite high compared to the recovery phase, although that ratio of peripheral blood mononuclear cells was not changed throughout the course. It was concluded that T lymphocytes and increased 2',5'-oligoadenylate synthetase activity in the cerebrospinal fluid may be one of the important components in the local inflammatory process independent of the systemic host defense mechanism in aseptic meningitis.

2',5'-Oligoadenylate Synthetase↗

Influence of early coronary reperfusion on QT interval dispersion after acute myocardial infarction.

We studied the influence of early coronary reperfusion on QT interval dispersion in patients with acute myocardial infarction (MI). There were 54 males and 18 females with a mean age of 60 +/- 10 years. Of the 51 patients with recanalization of the infarct related vessel in the recovery phase, 28 (group A) had early coronary reperfusion (5.5 +/- 2.7 hours), 23 other patients (group B) were not confirmed with early coronary reperfusion. Twenty-one patients (group C) did not undergo recanalization of the infarct related vessel in the recovery phase. Corrected QT (QTc) maximum, QTc minimum, and QTc dispersion calculated as the difference between the maximum and minimum QTc intervals, were compared among these three groups at both acute and recovery phase. At the acute phase after MI, there were no significant differences in the QTc maximum, QTc minimum, QT dispersion, and QTc dispersion among these three groups. At the recovery phase after MI, there were also no significant differences in the QTc maximum and QTc minimum. However, there were significant differences in the QT dispersion (0.035 +/- 0.010 in group A, 0.049 +/- 0.015 in group B, and 0.061 +/- 0.031 s in group C, respectively; P = 0.0001), and QTc dispersion (0.038 +/- 0.012 in group A, 0.050 +/- 0.015 in group B, and 0.063 +/- 0.032 s in group C, respectively; P = 0.0003) among the three groups. Comparison of QTc dispersion between acute and recovery phase revealed significant reduction from acute to recovery phase in group A. The number of premature ventricular contraction was lower in group A and B than group C. In summary, early coronary reperfusion may reduce electrophysiological instability by reducing QT dispersion in the recovery phase after acute MI.

Cardiac Catheterization↗

Recovery of the slow inward current from Ca2(+)-mediated and voltage-dependent inactivation in the rabbit sinoatrial node.

The process of recovery from inactivation of the slow inward current (isi) in the rabbit sinoatrial (S-A) node was evaluated by voltage clamp experiments using double microelectrode method. Double pulse experiments were carried out on preparations loaded with Cs+ using nystatin. The rate of the rapid isi inactivation depended on the amplitude of isi rather than the membrane potential. After a 50 ms depolarizing prepulse isi rapidly recovered from inactivation at -40 mV with a time constant of 84 +/- 25 ms, whereas after a longer prepulse, an additional slow recovery phase with a time constant of 1 to 2 s was observed. The amount of isi during the fast recovery phase following a 300 ms prepulse to -20 mV was smaller than that following a prepulse to +20 mV, as predicted by a Ca2(+)-mediated inactivation mechanism. Conversely, a prepulse to +20 mV caused a greater inactivation in the slow recovery phase, suggesting a voltage-dependent mechanism. The inactivation curve obtained during the fast recovery phase using 50 ms prepulses was U-shaped, indicating a predominant role of the Ca2(+)-mediated mechanism, whereas that obtained during the slow recovery phase resembled previously reported voltage-dependent steady state inactivation (f infinity) curve. These results indicate that the fast and slow phases of recovery represent the removal of Ca2(+)-mediated and voltage-dependent isi inactivation, respectively. The presence of Ca2(+)-mediated inactivation via steady state Ca2+ inflows was also suggested.

Animals↗

Prevalence, time course and malignancy of ventricular arrhythmia during spontaneous ischemic ST-segment depression.

Ventricular arrhythmias during transient myocardial ischemia were studied in 60 patients with spontaneous angina and greater than or equal to 1 ischemic attack with ST-segment depression during 24-hour ambulatory electrocardiography. The patients were divided into 2 groups: group 1, 10 patients (17%) who developed ventricular arrhythmias during 26 of 92 (28%) ischemic attacks; and group 2, 50 patients who did not show this phenomenon. Daily ischemic attacks, total ischemic time and the proportion of symptomatic ischemic attacks were significantly greater (p less than 0.01) in group 1 versus group 2. In group 1 patients, ischemic attacks were found to have twice the duration in the presence of arrhythmias than in their absence (20.4 +/- 11.9 vs 9.1 +/- 8.4 minutes, p less than 0.01); arrhythmias were more common during symptomatic than during silent ischemic attacks (39 vs 13%, p less than 0.02). Arrhythmias occurred at the onset or peak of ST-segment depression (ischemia phase) in 6 cases (60%), during the resolution of ST-segment depression (recovery phase) in 2 cases (20%) and during both phases of ischemic attacks in the remaining 2 (20%). When compared to recovery phase arrhythmias, ischemia phase arrhythmias were characterized by a later onset time (173 +/- 144 vs 58 +/- 54 seconds, p less than 0.01) and a longer duration (105 +/- 107 vs 41 +/- 22 seconds, p less than 0.01). During the ischemia phase, 16 of 353 ventricular premature complexes initiated ventricular tachycardia, while during the recovery phase only 1 of 161 ventricular premature complexes resulted in ventricular tachycardia (4.5 vs 0.6%, p less than 0.02). Thus, ventricular arrhythmias may accompany spontaneous ischemic ST-segment depression, when the latter is recurrent, prolonged and symptomatic; arrhythmias are characterized by a greater frequency, duration and malignancy during the ischemia phase than during the recovery phase of ischemic attacks.

Aged↗

Neural mechanisms of chromatic adaptation in L-type cone horizontal cells of the carp retina.

When a background light is delivered, the responsiveness of horizontal cells to light stimulus initially lowers but subsequently recovers gradually as shown by the increase in response amplitude to test light. These changes of responsiveness are observed when white or close wavelengths are used for both the background and test lights. However, the response amplitude to blue-green test light was initially enhanced but decreased and reached a steady state after the onset of red background illumination. The mechanism causing such a change of test responses was studied in the luminosity-type cone horizontal cells. The initial response enhancement was accompanied by an increase of the slope of hyperpolarizing phase, while the subsequent decrease of response amplitude was caused by the advancement of the recovery phase. The advancement of the recovery phase was eliminated by gamma-aminobutyric acid (GABA) or Co2+ (50 microM), which blocks GABA-induced currents in cone terminals. Dopamine, which inhibits GABA release from horizontal cells, stimulated the advancement of the recovery phase. The time course of the hyperpolarizing phase was not affected by these agents. The enhancement and the subsequent decrease of test responses were also observed in 6-hydroxydopamine-treated retinae. The results suggest that the GABAergic feedback pathway from horizontal cells to cones advances the recovery phase of response to test light. It appears, therefore, that the feedback modifies the responsiveness of horizontal cells to light stimulus under a red background illumination. The mechanism enhancing response amplitude will be also discussed.

Adaptation, Physiological↗

Cumulative characteristics of atracurium and vecuronium. A simultaneous clinical and pharmacokinetic study.

BACKGROUND: Cumulative effects (increased 25-75% recovery time with increasing dose) are evident with vecuronium but not with atracurium. Pharmacokinetic simulations suggest that vecuronium's cumulation occurs as recovery shifts from distribution to elimination whereas atracurium's recovery always occurs during elimination. The purpose of this study was to examine this pharmacokinetic explanation. METHODS: We assigned 12 volunteers to receive atracurium of vecuronium on three occasions during nitrous oxide-isoflurane anesthesia. Evoked adductor pollicis twitch tension was monitored. On occasion 1, the dose expected to produce 95% block (ED95) was estimated for each subject. On occasions 2 and 3, 1.2 or 3.0 multiples of ED95 were given as a bolus. Plasma was sampled for 128 min to determine muscle relaxant concentrations; pharmacodynamic modeling was used to determine effect-compartment drug concentrations (Ce). For each drug, recovery time, recovery phase half-life (rate of decrease in Ce during recovery), and Ce at 25% and 75% recovery were compared between doses. RESULTS: Atracurium's recovery time increased 2.4 +/- 2.2 min (mean +/- SD) with the larger dose, less than the increase with vecuronium (8.2 +/- 3.8 min). Atracurium's recovery phase half-life was 14.6 +/- 1.7 and 20.1 +/- 2.3 min with the small and large doses (P < 0.05); vecuronium's recovery phase half-life increased similarly from 13.5 +/- 2.3 to 18.5 +/- 5.0 min (P < 0.05). At 75% recovery, vecuronium's Ce decreased from 65 +/- 18 ng/ml with the small dose to 55 +/- 15 ng/ml with the large dose (P < 0.05). Assuming that neuromuscular junction sensitivity was constant, this difference could be explained by considering neuromuscular effects of vecuronium's metabolite, 3-desacetylvecuronium. CONCLUSIONS: Although vecuronium was cumulative (as predicted), atracurium was also slightly cumulative. Inconsistent with our hypothesis, recovery phase half-lives for both drugs increased similarly between doses; therefore, differences in cumulation were not solely explained by pharmacokinetics of the muscle relaxant. It appears that 3-desacetylvecuronium contributes to vecuronium's cumulative effect, even after usual clinical doses.

Adult↗

Influence of temperature on rheology of human erythrocytes.

The effect of variation in temperature on the rheological properties of human red blood cells was studied by determining the cell deformation in response to aspiration pressure applied via a micropipette. The time history of the deformation was analyzed by the use of a Voigt viscoelastic model consisting of an elastic element (E) in parallel with a viscous element (eta). Viscosity values were obtained during the initial rapid deformation phase (phase I), the later slow deformation phase (phase II), and the recovery phase. With a rise in temperature from 0 to 45 degrees C, both E and eta values decreased. A thermotropic transition temperature was found at approximately 21 degrees C for phase I viscosity and at approximately 9 degrees C for viscosity in the recovery phase, but not for phase II viscosity. These responses to temperature variations provide insights into the viscoelastic properties of the erythrocyte membrane.

Elasticity↗

Very low ethanol concentrations affect the viability and growth recovery in post-stationary-phase Staphylococcus aureus populations.

Pharmaceuticals, culture media used for in vitro diagnostics and research, human body fluids, and environments can retain very low ethanol concentrations (VLEC) (< or =0.1%, vol/vol). In contrast to the well-established effects of elevated ethanol concentrations on bacteria, little is known about the consequences of exposure to VLEC. We supplemented growth media for Staphylococcus aureus strain DSM20231 with VLEC (VLEC(+) conditions) and determined ultramorphology, growth, and viability compared to those with unsupplemented media (VLEC(-) conditions) for prolonged culture times (up to 8 days). VLEC(+)-grown late-stationary-phase S. aureus displayed extensive alterations of cell integrity as shown by scanning electron microscopy. Surprisingly, while ethanol in the medium was completely metabolized during exponential phase, a profound delay of S. aureus post-stationary-phase recovery (>48 h) was observed. Concomitantly, under VLEC(+) conditions, the concentration of acetate in the culture medium remained elevated while that of ammonia was reduced, contributing to an acidic culture medium and suggesting decreased amino acid catabolism. Interestingly, amino acid depletion was not uniformly affected: under VLEC(+) conditions, glutamic acid, ornithine, and proline remained in the culture medium while the uptake of other amino acids was not affected. Supplementation with arginine, but not with other amino acids, was able to restore post-stationary-phase growth and viability. Taken together, these data demonstrate that VLEC have profound effects on the recovery of S. aureus even after ethanol depletion and delay the transition from primary to secondary metabolite catabolism. These data also suggest that the concentration of ethanol needed for bacteriostatic control of S. aureus is lower than that previously reported.

Aerobiosis↗

Circulating activated T lymphocyte subsets in patients with silent thyroiditis.

In order to investigate the immunological aspects of silent thyroiditis, T lymphocyte subsets were analyzed by two-color flow cytometry in 10 patients with silent thyroiditis in the thyrotoxic phase, 12 patients with silent thyroiditis in the recovery phase, and 11 healthy volunteers as a control. The percentages of CD3+, CD4+, and CD8+ cells were similar in all three groups. In contrast, activated matured T (HLA-DR+CD3+), activated helper/inducer T (HLA-DR+CD4+) and activated suppressor/cytotoxic T (HLA-DR+CD8+) cells were more numerous in both the thyrotoxic and the recovery phases of patients with silent thyroiditis when compared with healthy controls. In a serial study of 6 patients with silent thyroiditis, the percentage of activated helper/inducer T (HLA-DR+CD4+) cells was higher in the thyrotoxic phase than in the recovery phase. These data indicate that the activation of T cells, especially of helper/inducer T cells, might be important for the induction of silent thyroiditis.

Adolescent↗