Quantum state features of the FEL radiation from the occupation number statistics.

The coherence of free-electron laser (FEL) radiation has so far been accessed mainly through first and second order correlation functions. Instead, we propose to reconstruct the energy state occupation number distribution of FEL radiation, avoiding the photo-counting drawbacks with high intensities, by means of maximum likelihood techniques based on the statistics of no-click events. Though the ultimate goal regards the FEL radiation statistical features, the interest of the proposal also resides in its applicability to any process of harmonic generation from a coherent light pulse, ushering in the study of the preservation of quantum features in general non-linear optical processes.

Effects of health at every size® interventions on health-related outcomes of people with overweight and obesity: a systematic review.

CONTEXT: The growing use of interventions based on the Health at Every Size® (HAES®) in obesity management. OBJECTIVE: This study aimed to summarize the health-related effects of HAES®-based interventions on people with overweight and obesity. DATA SOURCES: MEDLINE (via PubMed), EMBASE, Cochrane Library, LILACS, Google Scholar, OpenGrey and Grey Literature Report. STUDY SELECTION: A systematic review of studies published until January 2017 reporting on HAES®-based randomized and non-randomized controlled trials in people with overweight and/or obesity. DATA EXTRACTION: Fourteen papers met the inclusion criteria. The assessed studies included the following tests: blood profile, blood pressure, anthropometry, eating behaviour, energy intake, diet quality, psychological and qualitative evaluations. RESULTS: The HAES® interventions benefited both the psychological and physical activity outcomes, besides promoting behavioural and qualitative changes in eating habits. On the other hand, the results regarding cardiovascular responses, body-image perception and total energy intake were inconsistent. CONCLUSIONS: Despite improving the cardiovascular status, eating behaviours, quality of life and psychological well-being in participants, other large long-term clinical trials should be performed to establish the effectiveness of HAES®-based interventions in improving health for people with overweight and obesity. PROSPERO registration 2017: CRD42017054857.

Entropy production and non-Markovian dynamical maps.

In the weak-coupling limit approach to open quantum systems, the presence of the bath is eliminated and accounted for by a master equation that introduces dissipative contributions to the system reduced dynamics: within this framework, there are no bath entropy contributions to the entropy balance. We show that, as a consequence, the entropy production fails to be positive for a class of physically legitimate, that is completely positive and trace preserving, non-Markovian dynamical maps. Moreover, in absence of the semigroup property, if the reduced dynamics has a thermal asymptotic state, this need not be stationary. Then even the integrated entropy production becomes negative. These observations imply that, when the conditions leading to reduced dynamics of semigroup type are relaxed, a consistent formulation of the second law of thermodynamics requires that the environment contribution to the entropy balance be explicitly taken into account.

Objectively measured physical activity and its influence on physical capacity and clinical parameters in patients with primary Sjögren's syndrome.

Objective The objectives of this paper are to objectively measure habitual physical activity levels in patients with primary Sjögren's syndrome (pSS) with mild disease activity and to determine to which extent it may be associated with physical capacity and function and clinical features. Methods In this cross-sectional study, 29 women with pSS were objectively assessed for habitual physical activity levels (using accelerometry) and compared with 20 healthy women (CTRL) frequency-matched for physical activity levels, age, body mass index, and body fat percentage with regard to physical capacity and function, fatigue, depression, pain, and health-related quality of life. Results pSS showed 8.5 min/day of moderate-to-vigorous physical activity (MVPA) when only MVPA accumulated in bouts ≥ 10 min was considered; when considering total MVPA (including bouts < 10 min), average levels were 26.3 min/day, with 62% of pSS patients achieving the recommendation (≥ 21.4 min/day). Moreover, pSS showed lower VO2peak, lower muscle strength and function, higher fatigue, and poorer health-related quality of life when compared with CTRL ( p < 0.05). These differences (except for aerobic capacity) were sustained even when only individuals achieving the minimum of 21.4 min/day of total MVPA in both groups were compared. Finally, MVPA time was significantly correlated with aerobic conditioning, whereas total counts and sedentary time were associated with lower-body muscle strength and the bodily-pain domain of SF-36 in patients with pSS. Conclusion When compared to physical activity-matched healthy controls, pSS patients showed reduced physical capacity and function, increased fatigue and pain, and reduced health-related quality of life. Except for aerobic conditioning, these differences were sustained when only more physically active participants were compared, indicating that minimum recommended levels of physical activity for the general population may not be sufficient to counteract pSS comorbidities.

Correlations in quantum thermodynamics: Heat, work, and entropy production.

We provide a characterization of energy in the form of exchanged heat and work between two interacting constituents of a closed, bipartite, correlated quantum system. By defining a binding energy we derive a consistent quantum formulation of the first law of thermodynamics, in which the role of correlations becomes evident, and this formulation reduces to the standard classical picture in relevant systems. We next discuss the emergence of the second law of thermodynamics under certain-but fairly general-conditions such as the Markovian assumption. We illustrate the role of correlations and interactions in thermodynamics through two examples.

Effects of acute aerobic exercise on leukocyte inflammatory gene expression in systemic lupus erythematosus.

UNLABELLED: Systemic lupus erythematosus (SLE) is an autoimmune disease with a persistent systemic inflammation. Exercise induced inflammatory response in SLE remains to be fully elucidated. The aim of this study was to assess the effects of acuteexercise on leukocyte gene expression in active (SLEACTIVE) and inactive SLE (SLEINACTIVE) patients and healthy controls(HC). METHODS: All subjects (n = 4 per group) performed a 30-min single bout of acute aerobic exercise (~70% of VO2peak) on a treadmill, and blood samples were collected for RNA extraction from circulating leukocyte at baseline, at the end of exercise, and after three hours of recovery. The expression of a panel of immune-related genes was evaluated by a quantitative PCR array assay. Moreover, network-based analyses were performed to interpret transcriptional changes occurring after the exercise challenge. RESULTS: In all groups, a single bout of acute exercise led to the down-regulation of the gene expression of innate and adaptive immunity at the end of exercise (e.g., TLR3, IFNG, GATA3, FOXP3, STAT4) with a subsequent up-regulation occurring upon recovery. Exercise regulated the expression of inflammatory genes in the blood leukocytes of the SLE patients and HC, although the SLE groups exhibited fewer modulated genes and less densely connected networks (number of nodes: 29, 40 and 58; number of edges: 29, 60 and 195; network density: 0.07, 0.08 and 0.12, for SLEACTIVE, SLEINACTIVE and HC, respectively). CONCLUSION: The leukocytes from the SLE patients, irrespective of disease activity, showed a down-regulated inflammatory geneexpression immediately after acute aerobic exercise, followed by an up-regulation at recovery. Furthermore, less organized gene networks were observed in the SLE patients, suggesting that they may be deficient in triggering a normal exercised-induced immune transcriptional response.

Inflammatory cytokine kinetics to single bouts of acute moderate and intense aerobic exercise in women with active and inactive systemic lupus erythematosus.

The aim of this study was to evaluate changes in the cytokines INF-γ, IL-10, IL-6, TNF-α and soluble TNF receptors (sTNFR1 and sTNFR2) in response to single bouts of acute moderate and intense exercise in systemic lupus erythematosus women with active (SLE(ACTIVE)) and inactive (SLE(INACTIVE)) disease. Twelve SLE(INACTIVE) women (age: 35.3 ± 5.7 yrs; BMI: 25.6±3.4 kg/m2), eleven SLE(ACTIVE) women (age: 30.4 ± 4.5 yrs; BMI: 26.1±4.8 kg/m2), and 10 age- and BMI-matched healthy control women (HC) performed 30 minutes of acute moderate (~50% of VO(2)peak) and intense (~70% of VO(2)peak) exercise bout. Cytokines and soluble TNF receptors were assessed at baseline, immediately after, every 30 minutes up to three hours, and 24 hours after both acute exercise bouts. In response to acute moderate exercise, cytokines and soluble TNF receptors levels remained unchanged in all groups (P>0.05), except for a reduction in IL-6 levels in the SLE(ACTIVE) group at the 60th and 180th minutes of recovery (P<0.05), and a reduction in sTNFR1 levels in the HC group at the 90th, 120th, 150th, 180th minutes of recovery (P<0.05). The SLE(INACTIVE) group showed higher levels of TNF-α, sTNFR1, and sTNFR2 at all time points when compared with the HC group (P<0.05). Also, the SLE(ACTIVE) group showed higher levels of IL-6 at the 60th minute of recovery (P<0.05) when compared with the HC group. After intense exercise, sTNFR1 levels were reduced at the 150th (P=0.041) and 180th (P=0.034) minutes of recovery in the SLE(INACTIVE) group, whereas the other cytokines and sTNFR2 levels remained unchanged (P>0.05). In the HC group, IL-10, TNF-α, sTNFR1, and sTNFR2 levels did not change, whilst INF-γ levels decreased (P=0.05) and IL-6 levels increased immediately after the exercise (P=0.028), returning to baseline levels 24 hours later (P > 0.05). When compared with the HC group, the SLE(INACTIVE) group showed higher levels of TNF-α and sTNFR2 in all time points, and higher levels of sTNFR1 at the end of exercise and at the 30th minute of recovery (P<0.05). The SLE(ACTIVE) group also showed higher levels of TNF-α at all time points when compared with the HC group (P<0.05), (except after 90 min, 120 min and 24 hours of recovery) (P>0.05). Importantly, the levels of all cytokine and soluble TNF receptors returned to baseline 24 hours after the end of acute exercise, irrespective of its intensity, in all three groups (P>0.05). This study demonstrated that both the single bouts of acute moderate and intense exercise induced mild and transient changes in cytokine levels in both SLE(INACTIVE) and SLE(ACTIVE) women, providing novel evidence that acute aerobic exercise does not trigger inflammation in patients with this disease.

Branched-chain amino acids supplementation enhances exercise capacity and lipid oxidation during endurance exercise after muscle glycogen depletion.

AIM: It has been demonstrated that branched-chain amino acids (BCAA) transaminase activation occurs simultaneously with exercise-induced muscle glycogen reduction, suggesting that BCAA supplementation might play an energetic role in this condition. This study aimed to test whether BCAA supplementation enhances exercise capacity and lipid oxidation in glycogen-depleted subjects. METHODS: Using a double-blind cross-over design, volunteers (N.=7) were randomly assigned to either the BCAA (300 mg . kg . day -1) or the placebo (maltodextrine) for 3 days. On the second day, subjects were submitted to an exercise-induced glycogen depletion protocol. They then performed an exhaustive exercise test on the third day, after which time to exhaustion, respiratory exchange ratio (RER), plasma glucose, free fatty acids (FFA), blood ketones and lactate were determined. BCAA supplementation promoted a greater resistance to fatigue when compared to the placebo (+17.2%). Moreover, subjects supplemented with BCAA showed reduced RER and higher plasma glucose levels during the exhaustive exercise test. CONCLUSION: In conclusion, BCAA supplementation increases resistance to fatigue and enhances lipid oxidation during exercise in glycogen-depleted subjects.

Exercise training attenuates lipectomy-induced impaired glucose tolerance in rats.

OBJECTIVE: Since visceral adipose tissue (VAT) may account for impaired peripheral and hepatic insulin sensitivity (IS), it has been hypothesized that the partial removal of VAT could result in improved insulin action, while the re-growth of the excised tissue and/or compensatory growth of non-excised depots seems to occur. Thus, it was aimed to investigate whether or not VAT removal and exercise affect IS. METHODS: Male Wistar rats were fed a high-fat diet and subsequently assigned randomly to one of four groups: 1. exercised plus lipectomized (EL), 2. exercised plus sham-lipectomized (ES), 3. sedentary plus lipectomized (CL), 4. sedentary plus sham-lipectomized (CS). After lipectomy, EL and ES animals underwent a 7-consecutive-day training period. Body weight, food intake, basal metabolic rate, fasting glucose, and glucose tolerance were assessed before and after the interventions. Fasting insulin and the HOMA index, body fat mass, and the expression of pro-inflammatory genes were assessed after the interventions. RESULTS: EL group showed greater insulin sensitivity compared to all other groups. EL and ES groups showed lower fasting insulin levels when compared to CL and CS groups, respectively. The EL group showed improved IS when compared to the remaining groups. The CL group showed impaired glucose tolerance and increased TNF-alpha gene expression. Body weight and fat mass did not differ among the groups. PPAR gamma gene expression was increased in the EL and ES groups. CONCLUSIONS: These results showed that short-term swimming training improved insulin sensitivity, but failed to prevent fat regain in lipectomized animals. Lipectomy induced impaired glucose tolerance, which is probably related to increased TNF-alpha gene expression. It is possible that a high-fat diet might be implicated in faster regain of adipose tissue after lipectomy. Our results also show that short-term exercise associated with lipectomy could improve insulin sensitivity.

Swimming training down-regulates plasma leptin levels, but not adipose tissue ob mRNA expression.

The aim of the present study was to assess the effects of endurance training on leptin levels and adipose tissue gene expression and their association with insulin, body composition and energy intake. Male Wistar rats were randomly divided into two groups: trained (N = 18) and sedentary controls (N = 20). The trained group underwent swimming training for 9 weeks. Leptin and insulin levels, adiposity and leptin gene expression in epididymal and inguinal adipose tissue were determined after training. There were no differences in energy intake between groups. Trained rats had a decreased final body weight (-10%), relative and total body fat (-36 and -55%, respectively) and insulin levels (-55%) compared with controls (P < 0.05). Although trained animals showed 56% lower leptin levels (2.58 +/- 1.05 vs 5.89 +/- 2.89 ng/mL in control; P < 0.05), no difference in leptin gene expression in either fat depot was demonstrable between groups. Stepwise multiple regression analysis showed that lower leptin levels in trained rats were due primarily to their lower body fat mass. After adjustment for total body fat, leptin levels were still 20% (P < 0.05) lower in exercised rats. In conclusion, nine weeks of swimming training did not affect leptin gene expression, but did lead to a decrease in leptin levels that was independent of changes in body fat.

Swimming training down-regulates plasma leptin levels, but not adipose tissue ob mRNA expression

The aim of the present study was to assess the effects of endurance training on leptin levels and adipose tissue gene expression and their association with insulin, body composition and energy intake. Male Wistar rats were randomly divided into two groups: trained (N = 18) and sedentary controls (N = 20). The trained group underwent swimming training for 9 weeks. Leptin and insulin levels, adiposity and leptin gene expression in epididymal and inguinal adipose tissue were determined after training. There were no differences in energy intake between groups. Trained rats had a decreased final body weight (-10 percent), relative and total body fat (-36 and -55 percent, respectively) and insulin levels (-55 percent) compared with controls (P < 0.05). Although trained animals showed 56 percent lower leptin levels (2.58 ± 1.05 vs 5.89 ± 2.89 ng/mL in control; P < 0.05), no difference in leptin gene expression in either fat depot was demonstrable between groups. Stepwise multiple regression analysis showed that lower leptin levels in trained rats were due primarily to their lower body fat mass. After adjustment for total body fat, leptin levels were still 20 percent (P < 0.05) lower in exercised rats. In conclusion, nine weeks of swimming training did not affect leptin gene expression, but did lead to a decrease in leptin levels that was independent of changes in body fat.

Changes of gut microbiota and immune markers during the complementary feeding period in healthy breast-fed infants.

INTRODUCTION: Little is known about changes in intestinal microbiota during the important period of complementary feeding (weaning). This descriptive study investigated changes of selected gut microbiota and markers of gut permeability and the immune system in breast fed infants during the complementary feeding period. METHODS: 22 healthy, exclusively breast fed infants (from birth to 4 months) with no antibiotic intake during the month prior to the study, were followed from 4 to 9 months of age. Faecal and saliva samples were collected at the start of the study (V0) and at monthly intervals (V1-V5) for measurement of selective gut microbiota (bifidobacteria, lactobacilli, vancomycin-insensitive lactobacilli, enterobacteria, enterococci, Clostridium perfringens) using semi-selective media. Immune markers (alpha-1-antitrypsin, eosinophil cationic protein (ECP), secretory IgA and TNF-alpha were measured in saliva and secretory IgA and TNF-alpha in faecal samples. RESULTS: High stool bifidobacteria counts at the start of the study (7.99 1 1.95 log10 CFU/g faeces) remained stable throughout the 5 months of complementary feeding while counts of enterobacteria and enterococci increased with age (P < 0.05 and P = 0.02 respectively). Vancomycin-insensitive lactobacilli increased significantly during weaning for V0 to V3 (P < 0.01), and then decreased slightly (V4). Faecal Clostridium perfringens remained below the detection limit during the study and parameters measured in saliva did not change. Faecal ECP decreased significantly from 1.011.4 (V0) to 0.510.9 mg/mg protein (V5) P = 0.03. CONCLUSION: Age and/or diet modifications during complementary feeding had no impact on faecal bifidobacteria counts but increased those of enterobacteria and enterococci. Transient increases in faecal lactobacilli and vancomycin-insensitive lactobacilli counts were observed. The reduction in faecal ECP may indicate a decrease in gut permeability (reinforcement of gut mucosa integrity) during the weaning period with age [corrected]

Deregulation of the CD95/CD95L system in lymphocytes from patients with primary acute HIV infection.

OBJECTIVE: To analyze the role of CD95/CD95 ligand (CD95L) expression and functionality in peripheral blood lymphocytes (PBL) during primary, acute HIV syndrome (AHS) and in the subsequent period. PATIENTS: Twelve patients were studied during the acute phase of the viral infection and most were followed for some months. METHODS: Cell culture and cytotoxicity assays based upon 51Cr release and flow cytometry were used to evaluate cell killing via CD95 molecule, flow cytometry to assess surface antigens, enzyme-linked immunosorbent assay (ELISA) for the determination of soluble CD95 and CD95L plasma levels, quantitative competitive (QC) reverse transcription polymerase chain reaction (RT-PCR) with an original RNA competitor for the analysis of CD95L mRNA expression and QC RT-PCR for determining plasma viral load. RESULTS: The analysis of PBL during this phase revealed that almost all cells, including CD8 T cells with a virgin phenotype, B lymphocytes and natural killer cells displayed CD95 molecules on the plasma membrane. Activation of CD95 on the surface of isolated lymphocytes by anti-CD95 monoclonal antibodies or binding to CD95L induced rapid apoptosis. However, CD95L mRNA was not expressed in PBL from these patients and was poorly inducible. Soluble CD95 was found in the plasma of all patients, but only in a few at high levels, even some months after seroconversion. In contrast, soluble CD95L was detected in only one patient, this occurring after the symptomatic period. For 10 of the 12 patients, expression of CD95 on the cell membrane or in the plasma did not correlate with the plasma viral load, which varied widely from patient to patient. Further, plasma levels of soluble CD95 were not altered by decreased lymphocyte activation or by efficient antiretroviral therapy. CONCLUSIONS: In patients experiencing an acute, primary HIV infection, a prolonged deregulation of the CD95/CD95L system may exist, which is probably not entirely related to virus production but may contribute to the pathogenesis of the disease. The hypothesis can be put forward that a complex balance exists between proapoptotic events (increase in CD95 expression), probably triggered by the host as a method to limit viral production, and antiapoptotic events (decrease in CD95L expression) probably triggered by the virus as a way to increase its production and survival.

Differential down-regulation of CD95 or CD95L in chronically HIV-infected cells of monocytic or lymphocytic origin: cellular studies and molecular analysis by quantitative competitive RT-PCR.

We analysed the expression of CD95/CD95L in two widely used models for studying the cellular effects of chronic infection with human immunodeficiency virus type 1 (HIV-1), i.e. ACH-2 cells, derived from the lymphocytic cell line A301, and U1, derived from monocytic U937 cells. A301 and ACH-2 mounted the same amount of plasma membrane CD95, while U1 had a consistent decrease in CD95 expression. Using different antibodies, we failed to detect the plasma membrane form of its ligand, CD95L, but we could see the intracellular presence of that molecule in A301 cells and, to a lesser extent, in ACH-2 cells, but not in U937 or U1 cells. To confirm the cytofluorimetric data and quantify the expression of CD95L at the RNA level, we developed a quantitative competitive RT-PCR assay. The HUT78 cell line had about 50,000 copies mRNA/1000 cells, three times more after induction with a phorbol ester and ionomycin. ACH-2 expressed about 400- (basal) or 10- (induced) fold less CD95L mRNA than the parental cell line A301; U937 and U1 were below the limit of detection. In cells of lymphoid origin (ACH-2) chronic HIV infection inhibits the expression of CD95L, the phenomenon occurring at the transcriptional level. In cells of monocytic origin (U1) the infection decreases the plasma membrane expression of CD95. This suggests that HIV could trigger different anti-apoptotic strategies which likely depend upon the cell line which is infected. In monocytic cells which act as a viral reservoir, the expression of the molecule whose binding triggers apoptosis decreases, while in lymphoid cells, capable of exerting cytotoxicity, the expression of a molecule which induces apoptosis is reduced.

Apoptotic features of peripheral blood granulocytes and monocytes during primary, acute HIV infection.

Apoptosis plays a major role during HIV infection, including the primary, acute HIV syndrome (AHS), during which such phenomenon is massive. We asked whether apoptosis involved not only peripheral blood lymphocytes, but also monocytes (PBM) and granulocytes (PBG). Thus, we studied cells from different patients during the acute phase of the viral syndrome. The CD95 molecule was expressed at high density on the PBM and PBG surface during AHS. Culturing PBG for a few hours resulted in a significant membrane expression of phosphatidylserine, consistent with apoptosis. However, cells maintained for hours plasma membrane integrity and showed no relevant changes in mitochondrial membrane potential. The overexpression of CD95 was not associated with high plasmatic levels of sCD95 and, together with apoptosis and its related markers decreased after a few weeks of highly active antiretroviral therapy. During AHS, a deregulation of the CD95 system occurs in monocytes and granulocytes, is related to a high propensity of PBG to undergo apoptosis, and may contribute to the pathogenesis of the disease. Antiretroviral treatment resulted not only in a decrease of virus production, but also in a reduced PBG tendency to undergo spontaneous apoptosis. Even if the mechanism(s) responsible for this phenomenon remains to be elucidated, our data suggest a possible (indirect?) action of antiretroviral therapies on PBG and PBM which could explain, at least partially, the rescue of natural immunity and the reduced use of granulocyte-colony stimulating factor during such treatments.

Inhibition of proteasome function prevents thymocyte apoptosis: involvement of ornithine decarboxylase.

We have previously shown that polyamine levels rapidly decrease in thymocytes undergoing apoptosis, and that ornithine decarboxylase increases early but too transiently to maintain elevated polyamine levels. These data led us to suppose that a precocious ornithine decarboxylase degradation might be responsible for the imbalance of polyamine metabolism. Ornithine decarboxylase is known to be degraded by the cytosolic 26S proteasome that plays an essential role in thymocyte apoptosis. In this paper we demonstrate that the inhibition of proteasome function preserves ornithine decarboxylase activity and prevents thymocytes from undergoing apoptosis after dexamethasone treatment. Since intracellular polyamine levels are also preserved, ornithine decarboxylase seems to be functionally active in maintaining polyamine homeostasis after proteasome inhibition in thymocytes. Our proposed role for the proteasome in quiescent cells upon an apoptotic stimulus is to degrade proteins like ornithine decarboxylase that are involved in the control of the cell cycle and cell survival.

Successful immunosenescence and the remodelling of immune responses with ageing.

In recent decades, major theoretical and technological advances have been achieved in the field of immunology. These have allowed the scientific community to analyse the immune system in a much more sophisticated manner than was possible even 20 years ago. Moreover, great theoretical changes have also occurred in gerontology-in particular, the hypothesis has been put forward that ageing and diseases are two different phenomena, and that successful ageing, i.e. ageing in good psychophysical conditions, is really possible for most humans and animals. Immunosenescence was then carefully investigated, either in selected healthy people of advanced age or in the oldest old people, such as healthy centenarians. The main results showed that most immune parameters are indeed well preserved even at this far advanced age. This paper deals with some of the most important theoretical problems of immunosenescence. An immunological tenet was that the most important phenomenon of immunosenescence is the involution of the thymus. In most textbooks and papers it is taken for granted that the thymus starts its involution immediately after puberty. When people aged 60-65 were considered old, it was not difficult to think that they could live for the rest of their life with a fully involuted thymus. The findings on centenarians challenge this tenet, as they have only a small reduction of T lymphocytes, and a relatively normal number of virgin and memory T cells, together with a functional T cell repertoire. Other observations reported here on centenarians, concerning the activity of B lymphocytes and the cytokine network, as well as those on the well-preserved innate immunity and the cells' capability of undergoing proliferation after appropriate stimuli, suggest that complex immune changes occur with age, but also indicate that we have to modify our attitude, to grasp the new scenario which is emerging. Immunosenescence can no longer be considered as a unidirectional deterioration, and this complex phenomenon is much better described by terms such as 'remodelling', 'reshaping' or 'retuning'.

Is polyamine decrease a common feature of apoptosis? Evidence from gamma rays- and heat shock-induced cell death.

Here we report that in rat thymocytes undergoing apoptosis upon two different stimuli, such as heat shock treatment and gamma irradiation, an early mRNA accumulation of ornithine decarboxylase (ODC)--the rate-limiting enzyme of polyamine biosynthesis--was followed by a very marked increase in ODC activity (28-40 and 6-8-fold, respectively). However, polyamine levels started to decrease before the appearance of DNA laddering, being putrescine and spermidine strongly diminished (8-12 hs), and spermine even depleted (12 hs). Taken together with our previous data on another model of apoptosis, i.e., glucocorticoid-induced cell death (Desiderio et al., Cell Growth Differ. 6: 505-513, 1995), these results suggest that an imbalance of polyamine metabolism, i.e., a strong activation of ODC and a paradoxical decrease of the intracellular polyamine content, might be a general feature of the apoptotic process.