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Research in global change ecology relies heavily on global climatic grids derived from estimates of air temperature in open areas at around 2 m above the ground. These climatic grids do not reflect conditions below vegetation canopies and near the ground surface, where critical ecosystem functions occur and most terrestrial species reside. Here, we provide global maps of soil temperature and bioclimatic variables at a 1-km 2 resolution for 0-5 and 5-15 cm soil depth. These maps were created by calculating the difference (i.e. offset) between in situ soil temperature measurements, based on time series from over 1200 1-km 2 pixels (summarized from 8519 unique temperature sensors) across all the world's major terrestrial biomes, and coarse-grained air temperature estimates from ERA5-Land (an atmospheric reanalysis by the European Centre for Medium-Range Weather Forecasts). We show that mean annual soil temperature differs markedly from the corresponding gridded air temperature, by up to 10°C (mean = 3.0 ± 2.1°C), with substantial variation across biomes and seasons. Over the year, soils in cold and/or dry biomes are substantially warmer (+3.6 ± 2.3°C) than gridded air temperature, whereas soils in warm and humid environments are on average slightly cooler (-0.7 ± 2.3°C). The observed substantial and biome-specific offsets emphasize that the projected impacts of climate and climate change on near-surface biodiversity and ecosystem functioning are inaccurately assessed when air rather than soil temperature is used, especially in cold environments. The global soil-related bioclimatic variables provided here are an important step forward for any application in ecology and related disciplines. Nevertheless, we highlight the need to fill remaining geographic gaps by collecting more in situ measurements of microclimate conditions to further enhance the spatiotemporal resolution of global soil temperature products for ecological applications., (© 2022 The Authors. Global Change Biology published by John Wiley & Sons Ltd.)

Current analyses and predictions of spatially explicit patterns and processes in ecology most often rely on climate data interpolated from standardized weather stations. This interpolated climate data represents long-term average thermal conditions at coarse spatial resolutions only. Hence, many climate-forcing factors that operate at fine spatiotemporal resolutions are overlooked. This is particularly important in relation to effects of observation height (e.g. vegetation, snow and soil characteristics) and in habitats varying in their exposure to radiation, moisture and wind (e.g. topography, radiative forcing or cold-air pooling). Since organisms living close to the ground relate more strongly to these microclimatic conditions than to free-air temperatures, microclimatic ground and near-surface data are needed to provide realistic forecasts of the fate of such organisms under anthropogenic climate change, as well as of the functioning of the ecosystems they live in. To fill this critical gap, we highlight a call for temperature time series submissions to SoilTemp, a geospatial database initiative compiling soil and near-surface temperature data from all over the world. Currently, this database contains time series from 7,538 temperature sensors from 51 countries across all key biomes. The database will pave the way toward an improved global understanding of microclimate and bridge the gap between the available climate data and the climate at fine spatiotemporal resolutions relevant to most organisms and ecosystem processes., (© 2020 John Wiley & Sons Ltd.)

Permafrost controls geomorphological dynamics in maritime Antarctic ecosystems. Here, we analyze and model ground thermal regime in bordering conditions between continuous and discontinuous permafrost to better understand its relationship with the timing of glacial retreat. In February 2017, a transect including 10 sites for monitoring ground temperatures was installed in the eastern fringe of Byers Peninsula (Livingston Island, northern Antarctic Peninsula), together with one station recording air temperatures and snow thickness. The sites were selected following the Mid-Late Holocene deglaciation of the area at a distance ranging from 0.30 to 3.15 km from the current Rotch Dome glacier front. The transect provided data on the effects of topography, snow cover and the timing of ice-free exposure, on the ground thermal regime. From February 2017 to February 2019, the mean annual air temperature was -2.0 °C, which was >0.5 °C higher than 1986-2015 average in the Western Antarctic Peninsula region. Mean annual ground temperature at 10 cm depth varied between 0.3 and -1.1 °C, similar to the modelled Temperatures on the Top of the Permafrost (TTOP) that ranged from 0.06 ± 0.08 °C to -1.33 ± 0.07 °C. The positive average temperatures at the warmest site were related to the long-lasting presence of snow which favoured warmer ground temperatures and may trigger permafrost degradation. The role of other factors (topography, and timing of the deglaciation) explained intersite differences, but the overall effect was not as strong as snow cover., (Copyright © 2019 Elsevier Inc. All rights reserved.)

A new Circumpolar Active Layer Monitoring (CALM) site was established in 2009 at the Limnopolar Lake watershed in Byers Peninsula, Livingston Island, Antarctica, to provide a node in the western Antarctic Peninsula, one of the regions that recorded the highest air temperature increase in the planet during the last decades. The first detailed analysis of the temporal and spatial evolution of the thaw depth at the Limnopolar Lake CALM-S site is presented here, after eight years of monitoring. The average values range between 48 and 29cm, decreasing at a ratio of 16cm/decade. The annual thaw depth observations in the 100×100 m CALM grid are variable (Variability Index of 34 to 51%), although both the Variance Coefficient and the Climate Matrix Analysis Residual point to the internal consistency of the data. Those differences could be explained then by the terrain complexity and node-specific variability due to the ground properties. The interannual variability was about 60% during 2009-2012, increasing to 124% due to the presence of snow in 2013, 2015 and 2016. The snow has been proposed here as one of the most important factors controlling the spatial variability of ground thaw depth, since its values correlate with the snow thickness but also with the ground surface temperature and unconfined compression resistance, as measured in 2010. The topography explains the thaw depth spatial distribution pattern, being related to snowmelt water and its accumulation in low-elevation areas (downslope-flow). Patterned grounds and other surface features correlate well with high thaw depth patterns as well. The edaphic factor (E=0.05842m 2 /°C·day; R 2 =0.63) is in agreement with other permafrost environments, since frozen index (F>0.67) and MAAT (<-2°C) denote a continuous permafrost existence in the area. All these characteristics provided the basis for further comparative analyses between others nearby CALM sites., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The Antarctic Peninsula has had a globally large increase in mean annual temperature from the 1951 to 1998 followed by a decline that still continues. The challenge is now to unveil whether these recent, complex and somewhat unexpected climatic changes are biologically relevant. We were able to do this by determining the growth of six lichen species on recently deglaciated surfaces over the last 24 years. Between 1991 and 2002, when mean summer temperature (MST) rose by 0.42 °C, five of the six species responded with increased growth. MST declined by 0.58 °C between 2002 and 2015 with most species showing a fall in growth rate and two of which showed a collapse with the loss of large individuals due to a combination of increased snow fall and longer snow cover duration. Increased precipitation can, counter-intuitively, have major negative effects when it falls as snow at cooler temperatures. The recent Antarctic cooling is having easily detectable and deleterious impacts on slow growing and highly stress-tolerant crustose lichens, which are comparable in extent and dynamics, and reverses the gains observed over the previous decades of exceptional warming.

Axillary lymph node dissection remains an integral part of surgical treatment in patients with invasive breast cancer and axillary lymph node metastases. Chylous leakage after axillary lymph node dissection is infrequent. We report the case of a patient with an advanced local breast cancer that was subsidiary to surgery treatment after neoadjuvant chemotherapy. She had a postoperative chylous leakage; it was successfully treated conservatively in the postoperative course. Chylous leakage an infrequent complication alters axillary lymph node dissection, which has a conservative management in most published studies.

Aims: Lactic acid bacteria (LAB) are known to have antitumoral properties, although the intrinsic mechanisms responsible for the execution of this activity are poorly understood. Here, we investigated the ability of concentrated supernatants from Lactobacillus plantarum to promote cell death in a human promyelocytic cell line., Methods and Results: We aim to test the hypothesis that concentrated supernatants from Lact. plantarum at 5, 50 or 100 μg/ml for 24 h exert cytotoxic effects on HL-60 cells. Accumulation of reactive oxygen species (ROS) was diminished and nuclear staining with Hoechst 33342 and propidium iodide (PI) determined a necrotic induction in a concentrationdependent sequence. Concentrated supernatants did not modify or reduced the activity of caspase-3. The assessment of phosphatidylserine externalization by annexin V/PI double staining led to a necrotic state, but the treatment did not produce a dissipation of mitochondrial membrane potential (ΔΨm), whereas cell cycle analysis revealed that concentrated supernatants failed to significantly enhance the population of HL-60 cells in the hypodiploid (sub-G1) fraction., Conclusions: Concentrated supernatants from Lact. plantarum are capable of inducing necrosis rather than apoptosis at high doses in a promyelocytic cell line., Significance and Impact of the Study: Here, we demonstrate the cytotoxic properties of concentrated supernatants from Lact. plantarum on a tumor cell line, and then, to open the possibility to analyze the chemical composition to elucidate the bioactive molecules.

Objective: The ω-3 polyunsaturated fatty acids can suppress immune system functions. This property may cause adverse effects by impairing host resistance to infection. The present study focused on estimating the impact of different dietary lipids on the immune system of mice after a secondary infection with Listeria monocytogenes., Methods: BALB/c mice were divided into five dietary groups of olive oil, fish oil, sunflower oil, high-oleic sunflower oil, or low fat that was administered for 8 wk. The mice were immunized with 10(3) colony-forming units. Thirty-eight days later, each mouse was challenged with 10(4) colony-forming units. Mice survival and bacterial clearance from livers and spleens were determined. In addition, cytokine, chemokine, and adhesion molecule productions were quantified from the sera., Results: Survival percentage in mice fed a fish oil diet was 100% and bacterial numbers from spleen were decreased at 72 h. Interleukin-12, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 productions were decreased. Levels of tumor necrosis factor-α and interferon-γ were increased, whereas macrophage inflammatory protein-1α (MIP-1α) production was unaltered., Conclusion: Immune defense in mice fed a fish oil diet was improved after secondary exposure, acquiring an adequate resistance. This result could be attributable to an increase of a T-helper type 1 response., (Crown Copyright © 2011. Published by Elsevier Inc. All rights reserved.)

Natural antioxidants may be defined as molecules that prevent cell damage against free radicals and are critical for maintaining optimum health in both animals and humans. In all living systems, cells require adequate levels of antioxidant defenses in order to avoid the harmful effect of an excessive production of reactive oxygen species (ROS) and to prevent damage to the immune cells. During the inflammatory processes, the activation of phagocytes and/or the action of bacterial products with specific receptors are capable of promoting the assembly of the multicomponent flavoprotein NADPH oxidase, which catalyzes the production of high amounts of the superoxide anion radical (O(2)(-)). Under these particular circumstances, neutrophils and macrophages are recognized to produce superoxide free radicals and H(2)O(2), which are essential for defence against phagocytized or invading microbes. In this state, antioxidants are absolutely necessary to regulate the reactions that release free radicals. Antioxidant nutrients commonly included in the diet such as vitamin E, vitamin C, β-carotene, selenium, copper, iron and zinc improve different immune function exhibiting an important protective role in infections caused by bacteria, viruses or parasites. As a result, dietary antioxidants have been related to modulate the host susceptibility or resistance to infectious pathogens. Overall, numerous studies have suggested that the development of tolerance, and control of inflammation are strongly correlated with specific immune mechanisms that may be altered by an inadequate supply of either macronutrients or micronutrients. Therefore, the present paper will review the effects of dietary antioxidants on immune cell function and the impact on protection against infectious microorganisms.

Most antimicrobial peptides have been shown to have antitumoral activity. Cecropin A, a linear 37-residue antimicrobial polypeptide produced by the cecropia moth, has exhibited cytotoxicity in various human cancer cell lines and inhibitory effects on tumor growth. In this study, we investigated the apoptosis induced by cecropin A in the promyelocytic cell line HL-60. Treatment of cells with cecropin A was characterized by loss of viability in a dose-dependent manner, lactate dehydrogenase (LDH) leakage, and modest attenuation of lysosomal integrity measured by neutral red assay. An increase of reactive oxygen species (ROS) generation, DNA fragmentation, and phosphatidylserine externalization were quantified following cecropin A exposure at a concentration of 30 microM, whereas cecropin A-induced apoptosis was independent of caspase family members, because the activity of caspase-8 and -9 were irrelevant. Nevertheless, caspase-3 activity showed a significant increase at concentrations of 20-40 microM, but a considerable reduction at 50 microM. Flow cytometry analysis revealed a dissipation of the mitochondrial transmembrane potential (Deltapsi(m)), and the accumulation of cells at sub-G1 phase measured by FACS analysis of propidium iodide (PI) stained nuclei suggested induction of apoptosis. Morphological changes measured by Hoechst 33342 or acridine orange/ethidium bromide staining showed nuclear condensation, corroborating the apoptotic action of cecropin A. Overall, these data indicate that cecropin A is able to induce apoptosis in HL-60 cells through a signaling mechanism mediated by ROS, but independently of caspase activation., (Copyright 2010 Elsevier Inc. All rights reserved.)

Background: Selective biopsy of the sentinel ganglion (SBSG) has replaced axillary lymphadectomy (AL) as the procedure of choice in staging breast cancer in its initial stages and in clinically negative axilla. The aim of this study is to compare global event-free survival of those patients subjected to SBSG followed by AL, during the period of validation of the technique, with respect to those subjected to SBSG and AL if the sentinel ganglion (SG) showed metastasis., Methods: One hundred and forty-eight patients were included, 81 belonging to the period of validation and 67 to the clinical application group. Radiocoloid was administered intraperitumorally, obtaining images up until the visualisation of the SG; its identification and extirpation were carried out subsequently in the surgical intervention., Results: The efficacy of the technique in the validation group was 92.5%, sensitivity was 95.6% and the rate of false negatives was 4%. Of the 81 patients, 75 are free of disease (92.6%). Of the 67 patients belonging to the clinical application group, 63 (94%) are free of disease. No patient has presented axillary ganglion recurrence., Conclusion: In the validation of the technique we obtained values that fall within the demands of generally accepted quality. With an average follow up of 6 years we did not observe axillary ganglion recurrence in any of the two groups. There is no statistically significant difference in global and event free survival between the two groups.

Aims: The ability of concentrated supernatants from Lactobacillus plantarum to produce a disruption of plasma membrane in eukaryotic and prokaryotic cells has been examined., Methods and Results: A strain of Lact. plantarum (tolerant to acid and bile salts and resistant to several antibiotics) was used. It inhibited the growth of pathogenic Escherichia coli and L. monocytogenes. Supernatants from Lact. plantarum were concentrated by centrifugation. Either E. coli or HL-60 cells (a human promyelocytic cell line) were treated in the presence of the concentrated supernatants. The effect of concentrated supernatants from Lact. plantarum on E. coli growth demonstrated a bacteriostatic activity and a loss of cell viability measured by sytox green staining. Concentrated supernatants were capable of disturbing plasma membrane in E. coli and of promoting a cytotoxic and lyctic action on HL-60 cells and on human erythrocytes, respectively., Conclusions: These results suggest that Lact. plantarum release an effective compound responsible for an important effect in the disruption of E. coli plasma membrane and for a cytototoxic activity on promyelocytic leukaemia cells., Significance and Impact of the Study: This is the first in vitro study about the antimicrobial and biological activities of concentrated supernatants from Lact. plantarum.

Normal breast development is controlled by a balance between cell proliferation and apoptosis. The balance between the two parameters is crucial for determining the growth or regression of breast tumours in response to therapies and treatments. Therefore, it is necessary to understand the role of apoptosis in tumour progression. Active caspases participate as essential elements in the execution of apoptotic mechanisms. In the present study, we analysed the activities of caspase-3, -8 and -9 as well as cytochrome c release in N-methyl-nitrosourea (NMU)-induced rat mammary tumours, in order to establish the apoptotic events that occur in tumour growth in this animal model. Forty female virgin Wistar rats were randomly divided into two groups. One group was injected intraperitoneally with three doses of 50 mg/kg body weight of NMU. The control group received the vehicle only. After 122 days of NMU injection, the rats were sacrificed and the tumours were excised and processed. Results showed that in mammary tumours induced by NMU, the apoptotic death receptor-mediated pathway is activated through caspase-3 and -8, but the apoptotic mitochondrial pathway is suppressed through a non-activating process of caspase-9 activity, despite the release of cytochrome c. In conclusion, these findings have demonstrated a suppression of the apoptotic mitochondrial pathway through a non-activating process of caspase-9 activity, despite the release of cytochrome c in mammary tumours induced by NMU. Although the apoptotic death receptor-mediated pathway is activated, it is not enough to maintain the balance between proliferation and apoptosis, and thus determine the overall growth of the tumour.

The effects exerted by polyunsaturated fatty acids (PUFA) on immune system functions have been investigated in recent years. These studies have reported the important role that n-3 PUFA play in the diminution of incidence and severity of inflammatory disorders. Nevertheless, less attention has been paid to the action of monounsaturated fatty acids (MUFA) upon the immune system. The administration of a diet containing a high amount of olive oil in experimental animals produces a suppression of lymphocyte proliferation, an inhibition of cytokine production and a reduction in natural killer (NK) cell activity. Despite these alterations in immune functions, it has been reported that olive oil-rich diets are not as immunosuppressive as fish oil diets. An important aspect in immunonutrition is focused on the relationship between fats, the immune system and host resistance to infection, particularly when these nutrients are supplied to patients at risk of sepsis. Different studies have determined that olive oil-rich diets do not impair the host resistance to infection. Therefore, olive oil constitutes a suitable fat that may be applied in clinical nutrition and administered to critically ill patients. In the present review, we summarize the current knowledge on olive oil and immune system functions, the biological consequences derived from the administration of diets containing olive oil and the impact of olive oil on immune defence.

Background & Aims: Despite the beneficial effects in the resolution of inflammatory disorders due to their immunosuppressive properties, n-3 polyunsaturated fatty acids are associated with a reduction of immune resistance to some microorganisms. Here, we examine the influence of different dietary lipids on host immune resistance against Listeria monocytogenes in mice treated with cyclophosphamide (CPA)., Methods: Balb/c mice were fed one of four diets, which contained either olive oil (OO), fish oil (FO), hydrogenated coconut oil (HCO) or low fat (LF) for 4 weeks. Subsequently, mice were treated with CPA or PBS, prior to L. monocytogenes infection. Splenocyte proliferation, survival analysis, counts of viable bacteria from spleens and livers, and measurement of pro-inflammatory cytokine levels were determined., Results: The FO-rich diet reduced survival, particularly in CPA-treated mice. CPA was responsible for a significant increase of viable bacteria recovery from spleens and livers within each group fed high fat diets, which was aggravated in mice fed an FO diet. In addition, a significant increase of both TNF-alpha and IL-12p70 levels was detected in this group. These results may acquire a crucial relevance in clinical nutrition, particularly when FO diets are administered to immunocompromised patients., Conclusions: The mechanism(s) that impair(s) the elimination of L. monocytogenes could be associated with a low mitogen-stimulated splenocyte proliferation, and with an alteration of pro-inflammatory cytokine production. The application of the neutropenic agent CPA moderately aggravates the immunosuppressive state mainly in FO-fed animals.

Antimicrobial peptides have received increasing attention not only as potential candidates to their administration as antimicrobial agents, but also as potential drugs applied in cancer therapy. Here, we have examined the action of both nisin and magainin on human promyelocytic leukemia HL-60 cells. Cells were cultured in presence of either nisin or magainin 1 as well as in combination with both nisin and magainin 1. Results have revealed that magainin, but not nisin, produces a loss of cell viability in HL-60 cells, and a minor increase of hemolysis, whereas it is not responsible for cell membrane disruption and lactate dehydrogenase (LDH) leakage. In addition, magainin is involved in a significant generation of reactive oxygen species (ROS), as well as in an augment of caspase-3 activity. Magainin-induced apoptosis was verified by DNA fragmentation and annexin V-FITC/propidium iodide (PI) staining of the cells. Promotion of cell death by magainin occurs via cytochrome c release accompanied by a substantial increase of proteasome activity. These results underline the importance of magainin as a drug capable of exerting an in vitro antitumoral activity by triggering apoptosis.

Recent experimental observations have determined that long-chain n-3 polyunsaturated fatty acids suppress immune functions and are involved in the reduction of infectious disease resistance. BALB/c mice were fed for 4 weeks with one of four diets containing either olive oil (OO), fish oil (FO), hydrogenated coconut oil, or a low fat level. Interleukin-12p70 (IL-12p70), gamma interferon (IFN-gamma), and tumor necrosis factor alpha (TNF-alpha) production in the sera of mice fed these diets and challenged with Listeria monocytogenes were determined by enzyme-linked immunosorbent assay. In addition, bacterial counts from spleens of mice were carried out at 24, 72, or 96 h of infection. Here, we quantified an initial diminution of production of both IL-12p70 and IFN-gamma, which appear to play an important role in the reduction of host resistance to L. monocytogenes infection. In addition, an efficient elimination of L. monocytogenes was observed in spleens of mice fed a diet containing OO at 96 h of infection, despite reductions in IL-12p70 and TNF-alpha production, suggesting an improvement of immune resistance. Overall, our results indicate that the initial reduction of both IL-12 and IFN-gamma production before L. monocytogenes infection represents the most relevant event that corroborates the impairment of immune resistance by n-3 polyunsaturated fatty acids during the different stages of infection. However, we speculate that the modulation of other cytokines must be also involved in this response, because the alteration of cytokine production in mice fed an FO diet in a late phase of L. monocytogenes infection was similar to that in mice fed OO, whereas the ability to eliminate this bacterium from the spleen was improved in the latter group.

Several dietary lipids are capable of exerting an immunosupressor effect. This action may have undiserable effects on the host immune resistance to infectious diseases. The purpose of the present study was to determinate the immune status of mice fed dietary lipids and experimentally infected with a virulent strain of Listeria monocytogenes. Balb/c mice were divided into four groups and were fed with their respective diet: low fat diet (LF, 20%), olive oil diet (OO, 20%), fish oil diet (FO, 20%) and hydrogenated coconut oil (HCO, 20%). Mice were fed for four weeks and infected with L. monocytogenes by endovenous route. Results have shown a survival reduction in mice fed a diet containing FO, as well as a significant increase in the number of viable bacteria from spleen. In addition, we have observed an increase in the bactericidal activity in peritoneal cells from OO group, although the invasion of L. monocytogenes in cells from this group was larger. Finally, a significant reduction of lymphocyte proliferation was observed in the group fed an FO diet, whereas natural killer (NK) cell activity was not modified. These results indicate that dietary lipids constituted by polyunsaturated n-3 fatty acids reduce the murine immune resistance, whereas a diet constituted by OO-does not exert an immunosuppressor effect as relevant as FO diet, and it does not reduce the immune resistance leading to an efficient L. monocytogenes elimination.

The direct examination of the effects that fish oil diets (composed of long-chain n-3 polyunsaturated fatty acids) exert on immune system function indicates a reduction of host natural resistance to infectious diseases mainly because of a suppression of immune function generated by the fatty acids contained in this diet. Here, we evaluated the concentration of IL-12, IL-4, prostaglandin E2 and leukotriene B4 in the serum from BALB/c mice receiving four different diets. Each group was fed a diet that differed only in the source of fat: a low-fat diet (2.5% by weight), an olive oil diet (20% by weight), a fish oil diet (20% by weight) or a hydrogenated coconut oil diet (20% by weight). Mice were fed for 4 weeks and then infected with the intracellular pathogen Listeria monocytogenes. An initial reduction in the Th1-type response as a result of a decrease in IL-12p70 secretion, an inefficient action of IL-4 (Th2-type response) and no modification of pro-inflammatory lipid-mediator production could be, at least in part, the key events responsible for the inadequate elimination of L. monocytogenes from the spleens of mice fed a fish oil diet. Furthermore, our results suggest that the type of dietary lipids may affect the circulating concentration of IL-12p70 and IL-4, leading to a modulation in the protective cellular immune response to L. monocytogenes infection.

The potential action of certain fatty acids has been studied since the early 1970s. Numerous effects on immune system functions have been related to dietary lipid administration; therefore, several of them have been applied in the treatment of inflammatory disorders. Nevertheless, n-3 polyunsaturated fatty acids may affect host resistance to infectious diseases. In addition, several studies have demonstrated that certain fatty acids are involved in apoptosis induction. Here, we have examined the action of different dietary lipids on the promotion of apoptosis in thymocytes from mice fed with dietary lipids and infected with Listeria monocytogenes. Thus, L. monocytogenes promoted an important cytotoxic effect in all of the groups, but it did not increase the percentage of DNA fragmentation. Similarly, an important increase of caspase-3 activity was demonstrated in OO and FO groups, but infection with L. monocytogenes exerted an inhibitory effect. Finally, L. monocytogenes did not modify proteasome activity among groups fed with dietary lipids. On the basis of this preliminary study, we can state that the infection of thymocytes from mice fed with dietary lipids does not promote a synergistic effect in the induction of apoptosis. Hence, these results may partially serve to elucidate the immune mechanisms involved in cells from mice fed with dietary lipids in an infectious process.

Background: The involvement of certain fatty acids in the induction of apoptosis has been established recently. In fact, considerable attention has been given in the past few years to the participation of polyunsaturated fatty acids as substances capable of modulating tumor cell growth., Materials and Methods: Fatty acids such as eicosapentaenoic acid (EPA), linolenic acid (LNA), arachidonic acid (AA), linoleic acid (LA), oleic acid (OA) or stearic acid (SA) were added to YAC-1 tumor cells., Results: Incubation of cells with fatty acids revealed a loss of cell viability in a dose-dependent manner. Quantification of DNA fragmentation showed a significant increase particularly in cells treated in the presence of LA, whereas the accumulation of triacylglycerols in the form of cytoplasmic lipid droplets was significantly enhanced in cells cultured with EPA, LNA or AA. The production of reactive oxygen species (ROS) was substantially increased after cell incubation. Nevertheless, the analysis of caspase-3 activity indicated a relevant increase in cells cultured in the presence of LA, OA or SA, but not in cells cultured with EPA, LNA or AA., Conclusion: On the basis of these results, we can speculate that long-chain polyunsaturated fatty acids such as EPA and AA as well as LNA induce cell death in YAC-1 lymphoma by an independent mechanism of caspase-3 activation.

Background & Aims: Current knowledge of the potential effects that several dietary lipids exert on immune functions indicates that these substances participate actively in the modulation of immune system by which they contribute to the improvement of the conditions of patients suffering from inflammatory disorders. However, long-chain n-3 polyunsaturated fatty acids induce an immunosuppressive status that leads to a reduction of the host natural resistance to infectious agents as well as to an enhancement of oxidative damage. Hence, the present study has been designed to evaluate the effects on the immune system of the antioxidant N-acetyl-L-cysteine (NAC) in mice fed dietary lipids and infected with Listeria monocytogenes., Methods: Balb/c mice were fed for 4 weeks with diets containing either olive oil (OO, 20% by weight), fish oil (FO, 20% by weight) or hydrogenated coconut oil (HCO, 20% by weight). After dietary lipid administration mice were experimentally infected with L. monocytogenes or treated with NAC (25mg/ml intraperitoneally)., Results: NAC at a concentration of 1mM promoted a loss of cell viability, although no differences were observed among the four groups. After injection of NAC in combination with L. monocytogenes, 25% of mice fed a low-fat (LF) diet survived. However, in the groups fed dietary lipids no effect on survival of mice was found. NAC participated in the reduction of superoxide anion generation measured with nitroblue tetrazolium (NBT) in the group fed a FO diet. Finally, NAC reduced the recovery of L. monocytogenes from spleen of mice fed diets containing LF or HCO., Conclusions: On the basis of these results, we can confirm that the administration of NAC improves survival in mice fed LF diet, whereas a reduction in the generation of superoxide radicals was measured in mice fed a FO diet and infected with L. monocytogenes. Similarly, bacterial recovery was diminished in mice fed diets containing LF or HCO. Hence, these data reveal a beneficial effect of NAC in mice fed LF or HCO and a detrimental action of this antioxidant in mice fed diets containing FO or OO.

Nutritional status may have significant importance for the immune system, and particularly, unsaturated fatty acids may serve as modulators of immune functions. Clinical and epidemiological studies have demonstrated that fatty acids are involved in the reduction of the inflammatory processes that occur in diseases characterized by an overactivation of the immune system. At the same time, an increase in susceptibility to infection has also been reported. The importance of immune system modulation by dietary lipids in the presence of an intracellular bacterial pathogen, such as Listeria monocytogenes, was evaluated in the present study. BALB/c mice were divided into four groups which were each fed a low-fat (2.5% by weight) diet, an olive oil (OO; 20% by weight) diet, a fish oil (FO; 20% by weight) diet, or a hydrogenated coconut oil (HCO; 20% by weight) diet for 4 weeks. In each group, lymphocye proliferation was measured, and a reduction in the stimulation index was observed in the FO and HCO groups. Cytotoxicity exerted by L. monocytogenes was increased in the groups fed diets containing OO and FO after 6 h of incubation with the bacterium. An important increase in the production of reactive oxygen species was found in the groups fed the HCO diet after 12 h of incubation with L. monocytogenes. Finally, invasion and adhesion factors were not modified substantially by the action of dietary lipids, although these factors were reduced in cells from mice fed an FO diet. These results underline the importance of several dietary lipids as biological modulators of immune functions and their crucial role in the alteration of host natural resistance.

In recent years, it has been demonstrated that certain fatty acids are involved in the modulation of immune system functions. The mechanisms responsible for these effects are not fully elucidated, but many hypotheses have described numerous changes in the cell functionality as the main factors capable of altering the immune functions. In the present investigation, we have analysed the potential effects of FFA on cell viability, production of superoxide radicals or proteasome activity in assays in vitro. Thus, different FFA, such as OA, EPA or SA have been incorporated to cellular cultures at a concentration of 100 microM. Phospholipase, cyclooxygenase or lipooxygenase inhibitors abolished the loss of thymocyte viability exerted by EPA, the most immunosuppressive fatty acid. Similarly, measurement of the oxidative process by NBT reduction in cells treated with EPA was markedly increased. Nevertheless, the proteasome activity as a mechanism that participates in T-cell activation was not modified by direct action of the different fatty acids on the in vitro cultures. Overall, these results underline the differential role of several fatty acids (particularly long-chain n-3 polyunsaturated fatty acids) in order to modulate many functions of the immune system.

Over the past two decades, unsaturated fatty acids have received particular attention due to their ability to suppress immune functions. Nevertheless, suppression of immune functions also involves a reduction of host natural resistance to eliminate the infectious agents. We have analyzed the role of dietary lipids on immune functions in cells cultured with Listeria monocytogenes. Bactericidal efficiency of peritoneal cells from mice fed a fish oil diet against this bacterium was reduced and the incubation of peritoneal cells with polyunsaturated fatty acids led to similar results. The levels of superoxide radicals in the presence of L. monocytogenes increased in cells from mice fed olive oil or fish oil diets. Proteasome activity, a mechanism that participates in T cell activation, was inhibited in all of the dietary groups assayed in the presence of L. monocytogenes, but this inhibition was abolished in the presence of both MG132 (a proteasome inhibitor) and L. monocytogenes. Overall, these results underline the potential role of fatty acids in the modulation of many functions of the immune system.

Campylobacter jejuni has been reported to produce different toxins that may modulate the immune response in both animals and humans. The effect of C. jejuni enterotoxin on the immune response was investigated in two groups of Balb/c mice. One of them was inoculated intraperitoneally with 1010 colony forming units (CFU) of an enterotoxigenic strain (CCUG 7580), and the second one with a non-enterotoxigenic strain (CCUG 7440). The number of polymorphonuclear (PMN) cells from spleen increased in both enterotoxigenic and non-enterotoxigenic strains as a consequence of C. jejuni infection. Notwithstanding, lymphocyte proliferation stimulated by lipopolysaccharide (LPS) was increased by both enterotoxigenic and non-enterotoxigenic strains. Interleukin-2 (IL-2) production from splenic cells was increased significantly by infection with the enterotoxigenic strain. Both enterotoxigenic and non-enterotoxigenic strains reduced the splenic response to sheep erythrocytes; the response was significantly suppressed for immunoglobulin M (Ig M) and for immunoglobulin G (Ig G) synthesis. These results suggest that C. jejuni is able to modify some components of the immune response in mice, and also that the enterotoxigenic strain has more immunomodulating activity than the non-enterotoxigenic strain.

It is generally assumed that unsaturated fatty acids are important biological mediators that may be applied in the treatment of patients suffering from autoimmune disorders, in the modulation of tumorigenic processes or in the induction or inhibition of apoptosis. In this study, mice divided into three groups were fed dietary lipids; olive oil (20% w/w), fish oil (20% w/w) or hydrogenated coconut oil (20% w/w) for four weeks. Then, survival percentage, natural killer (NK) cell activity and lipid peroxidation were measured after murine lymphoma (LSTRA) transplantation. Survival percentage showed a reduced resistance to LSTRA tumor in mice fed fish oil diet and generaly loss of NK cell activity was observed after lymphoma transplantation. Lipid peroxidation from mice fed dietary lipids was measured in the presence of both phospholipase and cyclooxygenase inhibitors. In general, the data contained in this paper point to a detrimental effect caused by dietary lipids in mice transplanted with a lymphoma.

Nutritional status may exert a profound effect on immune system functions. Hence, several parameters of immune system are modified by dietary lipid administration, as lymphocyte proliferation, cytokine production, natural killer activity, antigen presentation, etc. Thus, numerous studies have indicated the key role of lipids as immune response modulators. These properties have been applied in the treatment of autoimmune and inflammatory diseases. As a result, the reduction or suppression of immune status due to lipid incorporation promotes an impairment in the ability of host natural response to eliminate infectious microorganisms as bacteria or parasites. In the present review, we analyze the current status about the relationship among dietary lipids, reduction of immune parameters and reduction of host natural response against infectious diseases. Many discrepancies are discussed, although several studies indicate a close association between dietary lipid manipulation and impairment in the elimination of bacteria, viruses or parasites. On the other hand, other studies point out a beneficial effect of dietary lipid manipulation on the host natural response. Future investigations will determine the events involved in the regulation of immune response by fatty acids and their role in the elimination of pathogenic agents.

Recent studies have suggested that antibiotics may act as biological response modifiers. In this study we investigated the effect of aztreonam, a monobactam antibiotic, on different parameters of acquired immunity in BALB/c mice. Different dosages of aztreonam injected into mice induced an increase in the lymphoproliferative response to specific mitogens and in the production of interleukin-2 by splenic cells, as well as a decreased response of this immune population to sheep erythrocytes lower total blood cell counts and a lower percentage of monocytes than in untreated mice. These results show a modulatory action of aztreonam on different immune parameters, which is independent of its antimicrobial activity and that could be of interest in human therapy.

Candida albicans is an increasingly important opportunistic fungal pathogen in immunocompromised patients. Natural killer (NK) cells constitute an important immune effector mechanism and are involved in the response to different pathological disorders. We wished to determine if this immune mechanism is involved in the specific response to C. albicans. Tilorone hydrochloride and related compounds have been described to display antiviral and antitumoral activity, as well as to enhance NK cell activity. In this study, we show the antimicrobial activity of different tilorone analogues and the enhanced resistance of tilorone-treated mice in experimental systemic candidiasis. We also present data suggesting that there is a correlation between NK cell activation and the resistance to experimental systemic candidiasis. Thus, it seems that the immunosurveillance of metastatic spread and the infection by C. albicans share some immune effector mechanisms, in particular activation of NK cells.

Current understanding based on the effect of dietary lipid manipulation upon immune system function indicates that fatty acids are involved in the modulation of the immune response through different and complex pathways. Reduction of several immune parameters by fatty acid action may be applied in the treatment of diseases characterised by an overactivation of the immune system. As a consequence, a reduction of host resistance against infectious agents has been reported in animals fed dietary lipids. The present study confirms the action of dietary lipids on the survival of mice infected with the pathogenic bacterium Listeria monocytogenes. A significant increase in peritoneal cells from mice fed a hydrogenated coconut oil diet was found, while a significant reduction of bacterial recovery from spleens of these mice was observed in this group. In addition, both eicosanoid and phospholipase inhibitors did not promote any modification of lymphocyte proliferation from mice fed olive oil or fish oil.

Dietary lipid manipulation may affect a great number of immune parameters, such as lymphocyte proliferation, cytokine synthesis, natural killer (NK) cell activity, phagocytosis and so on. The immunomodulation induced by dietary fatty acids may be applied in the amelioration of inflammatory disorders, such as autoimmune diseases. However, the mechanisms that participate in these processes are still poorly understood. It is probable that modulation of immune system by fatty acids of the diet may occur by alteration of membrane fluidity, lipid peroxide formation, eicosanoid production or regulation of gene expression. However, recent studies have reported the effects of several free fatty acids on apoptosis induction of in vitro cultures. In fact, a possible explanation of the effects that fatty acids promote on the immune system cells could be associated with an apoptotic process performed in an irreversible way. In vivo studies have demonstrated the ability of fatty acids to alter the survival of animals fed diets containing oils and infected with a pathogenic bacterium. Experimental infection in animals fed dietary lipids produces a modification of resistance to micro-organisms. The present review analyses all of these parameters that dietary fatty acids are capable of altering in order to modify the immune response. Further studies will be needed to establish the mechanisms involved in immune system regulation, reduction of symptoms derived from autoimmune pathologies and so on.

Mitochondrial membrane permeabilization is a critical event in the process leading to physiological or chemotherapy-induced apoptosis. This permeabilization event is at least in part under the control of the permeability transition pore complex (PTPC), which interacts with oncoproteins from the Bcl-2 family as well as with tumor suppressor proteins from the Bax family, which inhibit or facilitate membrane permeabilization, respectively. Here we show that thiol crosslinking agents including diazenedicarboxylic acid bis 5N, N-dimethylamide (diamide), dithiodipyridine (DTDP), or bis-maleimido-hexane (BMH) can act on the adenine nucleotide translocator (ANT), one of the proteins within the PTPC. ANT alone reconstituted into artificial lipid bilayers suffices to confer a membrane permeabilization response to thiol crosslinking agents. Diamide, DTDP, and BMH but not tert-butylhydroperoxide or arsenite cause the oxidation of a critical cysteine residue (Cys 56) of ANT. Thiol modification within ANT is observed in intact cells, isolated mitochondria, and purified ANT. Recombinant Bcl-2 fails to prevent thiol modification of ANT. Concomitantly, a series of different thiol crosslinking agents (diamide, DTDP, and BMH, phenylarsine oxide) but not tert-butylhydroperoxide or arsenite induce mitochondrial membrane permeabilization and cell death irrespective of the expression level of Bcl-2. These data indicate that thiol crosslinkers cause a covalent modification of ANT which, beyond any control by Bcl-2, leads to mitochondrial membrane permeabilization and cell death.

The immunomodulating properties of antimicrobial drugs may have important implications for clinical practice, particularly for those patients whose immune system has been compromised. In this study, we assessed the influence of different treatments with a beta-lactam antibiotic (imipenem/cilastatin) on several acquired immune responses of BALB/c mice; splenocyte responses to specific mitogens and to sheep red blood cells, IL-2 production and proportions of the different lympho-monocytic populations. Impenem/cilastatin was shown to modify some lymphocyte-associated immune functions and it would be useful to investigate whether immunomodulatory effects also occur in humans.

The effect of several Campylobacter jejuni strains on the immune response was analyzed in mice after intraperitoneal inoculation with 10(10) colony forming units (CFU). Three C. jejuni strains were assayed: CCUG 6968 (enterotoxigenic), CCUG 7580 (enterotoxigenic), and CCUG 7440 (non-enterotoxigenic). These C. jejuni strains induced a peritoneal inflammatory response and an important increase in the peritoneal phagocyte oxidative activity measured by chemiluminescence assay, as well as an increase in the number of peritoneal cells. Both interleukin-1 (IL-1) and tumor necrosis factor alpha (TNFalpha) production by peritoneal cells were not modified. However, C. jejuni 7440 caused a statistically significant increase in TNFalpha production. These results have demonstrated that different strains of C. jejuni induce an increase of the inflammatory response without a significant cytokine release. However, these infectious microorganisms may be eliminated efficiently by murine macrophages after phagocytosis.

The influence of the dose and the duration of treatment with aztreonam, a monocyclic beta-lactam antibiotic, on the natural immune response of mice has been investigated. The results show the effects induced by the antibiotic on several immune parameters were affected by the duration of treatment. Thus, treatment with 28 mg/kg per day of aztreonam over 14 days increased every immune parameter tested, while treatment with 57 mg/kg per day of aztreonam for 7 days only enhanced the natural killer (NK) activity of splenocytes. Since aztreonam does not apparently impair the innate immune response, it might be a suitable therapy for the treatment of patients who are immunosuppressed.

Apoptosis is accompanied by major changes in ion compartmentalization and transmembrane potentials. Thymocyte apoptosis is characterized by an early dissipation of the mitochondrial transmembrane potential, with transient mitochondrial swelling and a subsequent loss of plasma membrane potential (DeltaP sip) related to the loss of cytosolic K+, cellular shrinkage, and DNA fragmentation. Thus, a gross perturbation of DeltaPsip occurs at the postmitochondrial stage of apoptosis. Unexpectedly, we found that blockade of plasma membrane K+ channels by tetrapentylammonium (TPA), which leads to a DeltaP sip collapse, can prevent the thymocyte apoptosis induced by exposure to the glucocorticoid receptor agonist dexamethasone, the topoisomerase inhibitor etoposide, gamma-irradiation, or ceramide. The TPA-mediated protective effect extends to all features of apoptosis, including dissipation of the mitochondrial transmembrane potential, loss of cytosolic K+, phosphatidylserine exposure on the cell surface, chromatin condensation, as well as caspase and endonuclease activation. In strict contrast, TPA is an ineffective inhibitor when cell death is induced by the potassium ionophore valinomycin, the specific mitochondrial benzodiazepine ligand PK11195, or by primary caspase activation by Fas/CD95 cross-linking. These results underline the importance of K+ channels for the regulation of some but not all pathways leading to thymocyte apoptosis.

The effect of nisin on the immune response of mice was studied. Nisin (in the form of the commercial preparation Nisaplin) was incorporated in the diet of experimental mice which were fed for 30, 75 or 100 days. Short-term administration of diets containing Nisaplin induced an increase of both CD4 and CD8 T-lymphocyte cell counts and also a decrease of B-lymphocyte counts. After prolonged diet administration, T-cell counts returned to control levels. Normal levels of B-lymphocytes were also reached after prolonged administration of the lower (but not the higher) Nisaplin concentration. The macrophage/monocyte fraction isolated from peripheral blood became significantly increased after long-term administration (100 days) of Nisaplin-containing diets in a concentration-dependent way. Although the number of peritoneal cells was not affected by the diets, the phagocytic activity of peritoneal cells decreased after prolonged administration of low (but not high) Nisaplin doses.

The fatty acid palmitate can induce apoptosis. Here we show that the palmitate-induced dissipation of the mitochondrial transmembrane potential (Delta Psi m), which precedes nuclear apoptosis, is not prevented by inhibitors of mRNA synthesis, protein synthesis, caspases, or pro-apoptotic ceramide signaling. However, the mitochondrial and nuclear effects of palmitate are inhibited by overexpression of anti-apoptotic proto-oncogene product Bcl-2 and exacerbated by 2-bromo-palmitate as well as by carnitine. The cytoprotective actions of Bcl-2, respectively, is not antagonized by etomoxir, an inhibitor of carnitine palmitoyl transferase 1 (CPT1), suggesting that the recently described physical interaction between CPT1 and Bcl-2 is irrelevant to Bcl-2-mediated inhibition of palmitate-induce apoptosis. When added to purified mitochondria, palmitate causes the release of soluble factors capable of stimulating the apoptosis of isolated nuclei in a cell-free system. Mitochondria purified from Bcl-2 over-expressing cells are protected against the palmitate-stimulated release of such factors. These data suggest that palmitate causes apoptosis via a direct effect on mitochondria.

Previous studies have demonstrated that dietary lipid manipulation may modify immune response by affecting lymphocyte proliferation, phagocytosis, cytokine production, etc. In this paper, we investigated the effect of olive oil (OO) on the phagocytic activity and cytokine production by murine peritoneal cells. These results were compared with those obtained from mice fed diets containing sunflower oil (SO) or hydrogenated coconut oil (HCO). Balb/c mice were divided into three groups and fed diets containing 15% by weight of either OO, SO or HCO for 5, 15, 30, 60 or 90 d. Phagocytic activity and interleukin-1 (IL-1) production were increased in OO-fed mice as compared to the other groups. On the contrary, no significant differences were observed in the levels of tumor necrosis factor (TNF) production, although the levels of this cytokine were slightly increased in mice fed the OO diet. These observations suggest that OO is able to modify the immune response and therefore, it may be used as an immunomodulatory agent.

A mixture of Ficoll 400 and sodium diatrizoate (Hypaque) at a density of 1.077 g/ml has been used to isolate the mononuclear cells from the remaining haematic cells. A simple, inexpensive and classical method was established to obtain substantially erythrocyte-free polymorphonuclear cell preparations from mouse peripheral blood, using a mixture of the same substances but at a density of 1.119 g/ml. This method along with that at a density of 1.077 g/ml allows two cellular bands to appear which contain mononuclear and polymorphonuclear (PMN) cells, respectively. Using this method, the counts of monocytes isolated from peripheral blood are significantly greater than those obtained by a one-step Ficoll-Hypaque procedure. On the contrary, the counts of PMN cells are significantly smaller than when sedimentation in dextran (6% solution) is used after gradient centrifugation. In this paper, chemiluminescence assay has been used to analyze the possible variations in phagocytic activity of cells isolated by both procedures, since it appears to be one of the most sensitive methods available for this purpose. The results obtained show a slightly greater activation in monocytes and PMN cells isolated by one-step Ficoll-Hypaque procedure, in comparison with another method which uses both Ficoll-Hypaque 1077 and Ficoll-Hypaque 1119, although statistical differences were not significant.

The imipenem/cilastatin constitutes a broad spectrum beta-lactam antibiotic formulation, especially used in pre and post-operatory treatments for transplanted or drug-immunosuppresed patients. The effect of the dose and the duration of the treatment with imipenem/cilastatin on some parameters of natural immunity in BALB/c mice were examined. The treatment by intraperitoneal route with 1 or 2 g/70 kg/day during 7 days did not alter significantly the parameters tested, whereas the greater dose used (4 g/70 kg/day) had an inhibitory effect on peritoneal cell counts and phagocytic activity, as well as it caused an increase on IL-1 production and natural killer activity. The greater stimulating effect of innate immunity was obtained with the lowest imipenem/cilastatin dose used (0.5 g/70 kg/day). Since this antibiotic apparently does not impair the studied innate immune responses at 1 or 2 g/70 kg/day, it seems to be especially suited for the therapy of systemic bacterial infections in immunocompromised patients.