Listeria monocytogenes-associated respiratory infections: a study of 38 consecutive cases.

OBJECTIVES: Listeria monocytogenes (Lm) is a foodborne human pathogen responsible for severe infections, including septicaemia, neurolisteriosis, and maternal-foetal and focal infections. Little is known about Lm-associated respiratory tract or lung infections. METHODS: We conducted a retrospective study of culture-proven cases of Lm pleural infections and pneumonia reported to the French National Reference Centre for Listeria from January 1993 to August 2016. RESULTS: Thirty-eight consecutive patients with pleural infection (n = 32), pneumonia (n = 5), or both (n = 1) were studied; 71% of these were men. Median age was 72 (range 29-90). Two patients presented with concomitant neurolisteriosis. All patients but one reported at least one immunosuppressive condition (97%), with a median number of 2 (range 0-5), including 29% (8/28) with current exposure to immunosuppressive therapy and 50% (17/34) with ongoing neoplasia; 75% (21/28) reported previous pleural or pulmonary disease. Antibiotic therapy mostly consisted in amoxicillin (72%) associated with aminoglycoside in 32%. Chest-tube drainage was performed in 7/19 patients with empyema (37%); 25% of the patients (7/30) required intensive care management. In-hospital mortality reached 35% and occurred after a median time interval of 4 days (range 1-33 days). Three patients had recurrence of empyema (time interval of 1 week to 4 months after treatment completion). Altogether, only 13/31 patients (42%) diagnosed with Lm respiratory infection experienced an uneventful outcome at 2-year follow-up. CONCLUSION: Lm is a rare but severe cause of pneumonia and pleural infection in older immunocompromised patients, requiring prompt diagnosis and adequate management and follow-up.

Radiofrequency-induced carcinogenesis: cellular calcium homeostasis changes as a triggering factor.

The aim was to study the effects of radiofrequency (Rf) in a mice strain characterized by age-determined carcinogenesis of lymphatic tissues. Mice were treated with a 1?h/week Rf exposure for 4 months. A group submitted to sham exposure was used as control animals. The evolution of carcinogenesis was followed up to 18 months. The maximal life span of control mice was about 24 months. All dead animals were clinically and histologically examined to give an age-determined comparative quantification of the evolving carcinogenesis. A radiocalcium tracer method permitted the evaluation of Rf effects on transmembrane transport of extracellular calcium at 1 and 24 h after exposure. The determination of induced lipid peroxidation completed this second study. The findings show that Rf provoked an earlier general lymphocyte cell infiltration, formation of lymphoblastic ascites and extranodal tumours of different histological types, as well as an increased early mortality. The results suggest that in Rf-exposed mice, carcinogenesis may be induced earlier and with different pathological forms than in control animals. The modifications in cellular calcium homeostasis and the age-determined thymus involution appear to be important factors involved in this carcinogenesis process.

Relationship between the rate of gastric emptying and glucose and insulin responses to starchy foods in young healthy adults.

Twelve young healthy adults (five men, seven women) ingested four test meals on four occasions so we could examine the relationship between the rate of gastric emptying (GE) and the glucose response to different starchy foods. Each meal consisted of one food product containing 50 g starch: spaghetti, rice, French bread, or mashed potato. Basal and postprandial glucose and insulin responses were measured for 3 h. The foods were labeled with 3.7 MBq Tc99m-albumin and GE was studied by scintigraphy for 3 h. The rate of GE (expressed by the GE half-time) was fastest for mashed potatoes, then bread, rice, and slowest for spaghetti. Blood glucose and serum insulin responses were similar. A significant negative correlation was found between the GE half-time and the maximum variation in blood glucose level (r = -0.6, p less than 0.0001). The glucose response to all four foods is strongly related to the GE rate.

Mechanisms of gallium-67 accumulation by tumors: role of cell membrane permeability.

The effects of citrate ion on in vitro and in vivo uptake of [67Ga]citrate by tumor cells have been studied. Carrier-free [67Ga]citrate seems to follow the physical diffusion of citrate ions into the cell, and the presence of carrier gallium inhibits that diffusion, reducing considerably its uptake. These results appear to support the hypothesis that increased permeability of tumor cells is the principal cause of [67Ga]citrate accumulation by tumors.

Evaluation of peroral silicone dosage forms in humans by gamma-scintigraphy.

Gastric emptying of oral silicone dosage forms was studied in humans by gamma-scintigraphy. To achieve a constant and predictable residence time in the stomach, three different formulations based on known concepts such as controlled swelling were investigated. The importance of physical parameters such as size or shape were also examined to assess the feasibility of designing a dosage form for gastric retention. Three shapes: minimatrices, extruded rods and moulded slabs were screened. To label the silicone polymer, two isotopes, used routinely in nuclear medicine departments, were selected: iodine-123 and indium-111. To select the most suitable isotope, the yield and the stability of the labelling were determined in vitro on the pharmaceutical dosage forms. The residence time of these silicone formulations, labelled with iodine and administered in hard gelatine capsules, was monitored in 12 subjects with a gamma camera. The study was performed under fed conditions after ingestion of a standardised meal labelled with indium. The minimatrices provided at least 3 h retention, slabs exhibited 4 h 40 min retention. For the rods the mean residence time in the stomach was around 4 h 20 min. In addition, a correlation was established between the gastric emptying of rods and the half-gastric residence time of meal. On the contrary, such a correlation was not observed for the slabs.

Role of iron in lymphoma-induction by ATP.

Iron complexed by ATP induces lymphomas in mouse organs other than the specific targets of the lympho-adenitis provoked by sodium ATP: lymph nodes, spleen and liver. The reduction of life spans and the production of substantial volumes of ascites, that are lacking in the case of sodium ATP, are an index of the degree of malignancy of the induced lymphomas. On the basis of the known characteristics of iron-ATP complex of cellular calcium homeostasis alteration, the mechanism of these phenomena is discussed.

ATP in iron overload-induced intracellular calcium changes.

The cellular iron uptake from low molecular weight iron complexes (ferric citrate, ferric lactate and ferric ATP complex) is concentration-dependent, and only a small part of the iron penetrates the cell as shown by deferoxamine treatment. A threshold of iron concentration in the cell must be reached for the iron complex-induced increase of cellular Ca2+-uptake. ATP seems to play a key role in an iron translocation that enhances the effects of the iron complexes. A non-specific and competitive iron-binding by proteins seems to act as a buffer system that reduces the iron overload effects. Calcium channel blockers have no effects on the iron complex-cell interaction or iron-induced Ca2+-uptake modification. An iron complex concentration-dependent inhibition of the CaATPase activity, and its consequent Ca2+-extrusion impairment appear as the likely cause of calcium overload. The relevance of these findings in iron overload-induced pathologies is discussed.

Non-transferrin-bound iron and tumor cells.

The study of iron uptake from low molecular weight complexes by Ehrlich carcinoma cells shows concentration-dependence, and ATP increases the iron uptake from citrate and lactate complexes. Blood proteins can act as inhibitors, and deferoxamine chelation of cell-bound iron complex indicates that the percentage of iron penetrating the cell is about the same for a wide range of iron complex concentrations in the incubation medium (about 5% for ferric lactate). Ascorbic acid increases iron uptake and simultaneously decreases lipid peroxidation. Electrophoresis shows a very high iron transfer from ferric lactate to ATP, and to a lesser extent to ADP and AMP. In the pathological evolution of iron overload to a neoplasia, the probable involvement of an iron exchange between iron complexes from non-transferrin-bound iron of plasma and ATP is discussed.

Iron- and aluminum-induced carcinogenesis.

Ferric and aluminum complexes with ATP have shown the induction of tumors in the site of subcutaneous injection, whereas sodium ATP has not. A concomitant but apparently independent phenomenon was a severe lymphoadenitis. The tumor calcium concentration showed an inverse relationship with the tumor growth rate. Carcinogenesis and lymphoadenitis are discussed considering well known effects of ferric and aluminum complexes with ATP on the cellular calcium homeostasis and of ATP on lymphatic tissue proliferation.

Comparison of the biodistribution in mice of 111indium oxine encapsulated into poly(lactic-co-glycolic)-D,L-85/15 and poly(epsilon caprolactone) nanocapsules.

Poly(lactic-co-glycolic)-D,L-85/15 (PLAGA) nanocapsules and poly(epsilon caprolactone) (PCL) nanocapsules were labeled with a relatively long half-life compound that is usually used in humans; that is, 111In-labelled oxine (111In oxine). This labeling technique led to a high 111In oxine entrapment efficiency and good stability during dialysis against phosphate buffer and phosphate buffered albumin solution. Because of these characteristics, the nanocapsules biodistribution was followed up after intravenous administration for up to 96 h by determining the gamma activity in the tissues after sampling. The administration of the PCL-encapsulated 111In oxine led to a decrease in the blood radioactivity and an increase in the liver radioactivity compared with the solution. This effect was even more pronounced with the PLAGA nanocapsules. Finally, the activity level in other tissues, such as the kidneys, the lungs, and the spleen, appeared to be rather low and only slightly affected by the encapsulation into one or the other polymer.

On the role of transferrin in 67Ga uptake by tumor cells.

In vitro uptake of 67Ga-citrate and 59Fe-citrate by DS sarcoma cells in the presence of tumor-bearing animal blood plasma showed a dramatic inhibition of both 67Ga and 59Fe uptakes: about 1/10 of 67Ga and 1/50 of the 59Fe are taken up by the cells. Subcellular fractionation appears to indicate no specific binding to cell structures, and the difference of binding seems to be related to the transferrin chelation and transmembrane transport differences.

Study of competitive binding of gallium and iron by tumor cells.

The influence of iron and gallium carriers on the in vitro and in vivo uptake of 67Ga and 59Fe by tumor cells has been studied. The results appear to indicate that ferritin might be involved in most of the systemic accumulation of 67Ga but that the mechanism of tumor uptake might be different.

Iron-binding proteins and 67Ga accumulation by tumor cells.

Tumor cells incubated with 67Ga-citrate plus lactoferrin showed a lactoferrin concentration-dependent increase of 67Ga uptake while for transferrin the effect was an inhibition. A correlation was observed between the binding of 131I-labelled lactoferrin or 131I-labelled transferrin and the uptake of 67Ga by the cells. Saturation with iron did not change significantly the effects of the iron-binding proteins. Preincubation with lactoferrin, transferrin or ferric citrate increased 67Ga uptake. The formation of a ternary complex in which 67Ga mimics iron is discussed.

On the mechanisms of 67Ga and 59Fe uptake by tumors.

The uptake of 67Ga-citrate and 59Fe-citrate in the presence or absence of gallium and iron carriers, was studied on DS-sarcoma-bearing rats. Differences of uptake pattern were observed with both radionuclides. The tumor uptake of 67Ga is greatly affected by both carriers while 59Fe uptake is independent of the presence of carriers. The role of isotopic dilution, ionic competition, and the probable presence of high and low affinity binding sites in this phenomenon are discussed.

Tumor uptake of high and low molecular weight fractions from 67Ga-citrate labelled blood plasma.

Blood plasma from tumor-bearing rats was incubated with 67Ga-citrate, and two fractions of high molecular weight (proteins) and low molecular weight were isolated by dialysis and by gel-filtration chromatography. Both fractions showed a different in vivo uptake by DS-sarcoma-bearing animals, the high molecular weight fraction being accumulated to a lesser extent. Compared to 67Ga-citrate the low molecular weight fraction showed a different uptake which for most tissues was significatively higher. This behavior suggests the presence of 67Ga in chemical forms other than citrate in the low molecular weight fraction. The lower uptake of the blood protein fraction is discussed.

Long-term oral administration of aluminum in mice. Aluminum distribution in tissues and effects on calcium metabolism.

Six months of oral administration of aluminum lactate provokes an important accumulation of aluminum in various tissues of mice. The accumulation magnitude order is spleen > kidney > brain > liver > blood. No systemic toxic effects (weight loss or neurolytic effects) were observed. Values of calcium content and 45Ca-uptake by the different tissues showed no modifications of calcium metabolism. The lack of calcium homeostasis modification caused by a probable aluminum insolubilization, and the incidence of other individual factors on individual deviations from group behavior is discussed.

Effects of iron complexes on brain calcium homeostasis.

The effects of two physiological low molecular weight iron complexes, ferric lactate and ferric adenosine triphosphate (ATP) on brain Ca2+ homeostasis modification, have been studied in vitro and in vivo. In vitro ferric ATP complex shows a higher efficiency as modifier of Ca2+ homeostasis. This higher reactivity and the in vivo observed effect of increased brain uptake of iron from ferric lactate provoked by the presence of ATP, corroborate in vitro results showing an iron transfer from ferric lactate to ATP, as well as the mediator role of ATP in the iron-induced cellular Ca2+ homeostasis modification process. The possible role of this process in Parkinson's disease is discussed.

Liver calcium homeostasis modification by iron: a probable factor in its carcinogenesis.

Low molecular weight iron complexes, ferric lactate and ferric-ATP complex, induce an important increase of Ca(2+)-uptake by liver. The activity of ferric lactate increased by the presence of sodium ATP, and the steady high effect of ferric-ATP complex appear to indicate that ATP might play an important role in the in vivo formation of low molecular weight iron complexes that can induce the modification of the hepatocytes calcium homeostasis, the event that might be one of the factors triggering the malignant transformation.

Modification of in vivo Ca(2+)-uptake by parenterally administered aluminum complexes.

The parental administration of complexed aluminum induces a very significant increase of Ca(2+0-uptake by various tissues. The effects are more important with aluminum-ATP complex than with the simultaneous administration of aluminum lactate and sodium ATP. In the last case the increase in calcium uptake does not reach the many fold (up to 7 times) values observed with aluminum-ATP complex. In this aluminum-induced modification of cellular calcium homeostasis ATP appears to act as a mediator of the metal complex effects. These experimental results emphasize the importance of the role of ATP in the biological properties of low molecular weight metal complexes.

Iron-ethanol synergism and pathological liver transformation.

The synergistic effects of iron overload and ethanol on the liver of mice were studied over a period of 46 weeks. The determination of several parameters (iron, calcium, magnesium, alpha-hydroxyproline, lipid peroxidation, hepatomegalic and splenomegalic indexes) showed that ferrous and ferric lactates provoke an increase of calcium in the liver, higher than that of ethanol in the control animals. The relationship between liver calcium homeostasis modification and the increase of collagen and lipid peroxidation is discussed. Histological examinations showed differences in the tissular characteristics especially when iron and ethanol were given together. These findings suggest the liver calcium homeostasis changes found as a synergistic effect in the early stages of chronic iron overload may be of importance as a trigger of events leading to the pathway of fibrosis-->cirrhosis-->hepatocarcinoma reported in pathologies such as nutritional siderosis and hemochromatosis.