Increased Ion Temperature and Neutron Yield Observed in Magnetized Indirectly Driven D_{2}-Filled Capsule Implosions on the National Ignition Facility.

The application of an external 26 Tesla axial magnetic field to a D_{2} gas-filled capsule indirectly driven on the National Ignition Facility is observed to increase the ion temperature by 40% and the neutron yield by a factor of 3.2 in a hot spot with areal density and temperature approaching what is required for fusion ignition [1]. The improvements are determined from energy spectral measurements of the 2.45 MeV neutrons from the D(d,n)^{3}He reaction, and the compressed central core B field is estimated to be ∼4.9 kT using the 14.1 MeV secondary neutrons from the D(T,n)^{4}He reactions. The experiments use a 30 kV pulsed-power system to deliver a ∼3 µs current pulse to a solenoidal coil wrapped around a novel high-electrical-resistivity AuTa_{4} hohlraum. Radiation magnetohydrodynamic simulations are consistent with the experiment.

Targeting the tumour microenvironment in platinum-resistant ovarian cancer.

Ovarian cancer typically presents at an advanced stage, and although the majority of cases initially respond well to platinum-based therapies, chemoresistance almost always occurs leading to a poor long-term prognosis. While various cellular autonomous mechanisms contribute to intrinsic or acquired platinum resistance, the tumour microenvironment (TME) plays a central role in resistance to therapy and disease progression by providing cancer stem cell niches, promoting tumour cell metabolic reprogramming, reducing chemotherapy drug perfusion and promoting an immunosuppressive environment. As such, the TME is an attractive therapeutic target which has been the focus of intense research in recent years. This review provides an overview of the unique ovarian cancer TME and its role in disease progression and therapy resistance, highlighting some of the latest preclinical and clinical data on TME-targeted therapies. In particular, it focuses on strategies targeting cancer-associated fibroblasts, tumour-associated macrophages, cancer stem cells and cancer cell metabolic vulnerabilities.

Immunohistochemical Analysis of BRAF (V600E) Mutation and P16 Expression in Malignant Melanoma in Lagos, Nigeria: A 10-Year Retrospective Study.

BACKGROUND: In Blacks, malignant melanoma (MM) is associated with greater morbidity and mortality compared to Caucasians. MMs with BRAF V600E mutation as well as those with loss of p16 protein expression are associated with aggressive behavior and worse prognosis. OBJECTIVES: We determined BRAF (V600E) mutation status and loss of p16 expression in MM cases in Lagos, Nigeria, and correlated these with histopathologic parameters and patients' age. METHODS: Forty-five cases of MM received between January 2005 and December 2014 in the Anatomic and Molecular Pathology Department of Lagos University Teaching Hospital were subjected to immunohistochemical studies to determine BRAF V600E mutation and p16 protein expression. These included cutaneous (n=37), musosal (n=3), and ocular MM (n=2) as well as lymph node metastatases (n=3). RESULTS: BRAF (V600E) mutations were detected in 5/45 (11%) while 31/45 (69%) of the cases had loss of p16 expression. No statistically significant association was found between the BRAF (V600E) mutation, loss of p16 expression, and histologic parameters such as histologic variant, Clark level, Breslow thickness, and ulceration. CONCLUSION: BRAF (V600E) mutation was detected only in a small proportion of cases while loss of p16 expression occurred in most cases which also had high Clark level, high Breslow thickness, and ulceration.

Three-dimensional digital reconstruction of human placental villus architecture in normal and complicated pregnancies.

OBJECTIVE: This study aimed to examine the use of digital technology in the three-dimensional reconstruction of human placentas. STUDY DESIGN: Placentas obtained at term elective caesarean section were sampled, formalin-fixed and embedded in paraffin. Two hundred 5 µm consecutive sections were cut from each specimen and the resultant slides stained with haematoxylin and eosin. Slides were then scanned and the digitised images reconstructed using customised software. RESULTS: Three-dimensional reconstructions were successfully achieved in placentas from normal pregnancies and those complicated by pre-eclampsia, growth restriction, and gestational diabetes. Marked morphological differences were readily identifiable, most clearly in the stem villus architecture. CONCLUSION: This method is an emerging research tool for examining placental histoarchitecture at high resolution and gaining clinically relevant insight into the placental pathology allied to pregnancy complications such as PET, IUGR and GD.

Preoperative neutrophil:lymphocyte and platelet:lymphocyte ratios predict endometrial cancer survival.

BACKGROUND: Variations in systemic inflammatory response biomarker levels have been associated with adverse clinical outcome in various malignancies. This study determined the prognostic significance of preoperative neutrophil:lymphocyte (NLR), platelet:lymphocyte (PLR) and monocyte:lymphocyte (MLR) ratios in endometrial cancer. METHODS: Clinicopathological and 5-year follow-up data were obtained for a retrospective series of surgically treated endometrial cancer patients (n=605). Prognostic significance was determined for overall (OS) and cancer-specific survival (CSS) using Cox proportional hazards models and Kaplan-Meier analysis. Receiver-operator characteristic and log-rank functions were used to optimise cut-offs. NLR, PLR and MLR associations with clinicopathological variables were determined using non-parametric tests. RESULTS: Applying cut-offs of ⩾2.4 (NLR), ⩾240 (PLR) and ⩾0.19 (MLR), NLR and PLR (but not MLR) had independent prognostic significance. Combining NLR and PLR scores stratified patients into low (NLR-low and PLR-low), intermediate (NLR-high or PLR-high) and high risk (NLR-high and PLR-high) groups: multivariable hazard ratio (HR) 2.51; P<0.001 (OS); HR 2.26; P<0.01 (CSS) for high vs low risk patients. Increased NLR and PLR were most strongly associated with advanced stage (P<0.001), whereas increased MLR was strongly associated with older age (P<0.001). CONCLUSION: Both NLR and PLR are independent prognostic indicators for endometrial cancer, which can be combined to provide additional patient stratification.

Epithelial and stromal-specific immune pathway activation in the murine endometrium post-coitum.

The endometrium is a dynamic tissue, demonstrating cyclical growth/remodelling in preparation for implantation. In mice, seminal constituents trigger mechanisms to prepare the endometrium, a process dubbed 'seminal priming' that modifies immune system components and mediates endometrial remodelling in preparation for pregnancy. An array of cytokines has been reported to mediate this interaction, although much of the literature relates to in vitro studies on isolated endometrial epithelial cells. This study measured changes in immune-related gene expression in endometrial epithelial and stromal cells in vivo following natural mating. CD1 mice were naturally mated and sacrificed over the first 4 days post-coitum (n=3 each day). Endometrial epithelial and stromal compartments were isolated by laser capture microdissection. Labelled cRNA was generated and hybridised to genome-wide expression microarrays. Pathway analysis identified several immune-related pathways active within epithelial and stromal compartments, in particular relating to cytokine networks, matrix metalloproteinases and prostaglandin synthesis. Cluster analysis demonstrated that the expression of factors involved in immunomodulation/endometrial remodelling differed between the epithelial and stromal compartments in a temporal fashion. This study is the first to examine the disparate responses of the endometrial epithelial and stromal compartments to seminal plasma in vivo in mice, and demonstrates the complexity of the interactions between these two compartments needed to create a permissive environment for implantation.

Interleukin-4 -590 (C>T), toll-like receptor-2 +2258 (G>A) and matrix metalloproteinase-9 -1562 (C>T) polymorphisms in pre-eclampsia.

Functional single nucleotide polymorphisms (SNPs) of interleukin (IL)-4 -590 (C>T), toll-like receptor (TLR)-2 +2258 (G>A) and matrix metalloproteinase (MMP)-9 -1562 (C>T) were examined by polymerase chain reaction-restriction fragment length polymorphism to identify their merit as genetic markers for pre-eclampsia. One hundred and seventeen pre-eclamptic women and 146 control subjects with uncomplicated singleton pregnancies participated in this study, conducted at Leeds General Infirmary and St James's University Hospital. While the TLR-2 +2258 (G>A) and MMP-9 -1562 (C>T) SNPs failed to present any significant association with pre-eclampsia, there was a marked trend for an association between the IL-4 -590 (C>T) SNP and pre-eclampsia (chi(2)= 5.87, P = 0.055), with a prevalence of TT homozygous women in this group (OR 4.455, 95% CI 1.286-15.350).

[The teaching of microbiology in the Faculty of Medicine of the University of Rome. Memories of the Institute]. / L'insegnamento di Microbiologia nella Facoltà di Medicina dell'Università di Roma. Amarcord di un Istituto.

The Author describes the various phases of the teaching of microbiology in the Faculty of Medicine of the University, of Rome, from the unity of Italy to the end of the twentieth century. A regular course of Bacteriology was started only in the academic year 1905/1906 as separate teaching from that of Hygiene and the Institute of Bacteriology was created in 1924. It was centered in Piazza del Viminale in Rome, in the same building as the Institute of Hygiene. Prof Vittorio Puntoni was the first Director of the Institute, also in its new site of the Città Universitaria which was inaugurated in 1935. In the meantime the old name of Bacteriology was changed to Microbiology and prof Puntoni remained as Director until 1943. The bombing during the war produced heavy damage to the new Institute and with the appointment of prof Aldo Cimmino as a new Director in 1946 the Institute of Microbiology began a long period of reconstruction and development. An astonishing improvement was achieved in the availability of human and technical resources, many groups of research workers were created and several pupils became professor of Microbiology in different Italian Universities. In 1981 prof Cimmino definitely retired, leaving, the teaching of Microbiology in the Faculty of Medicine of the University of Rome "La Sapienza" to five of his pupils. One of them, prof Garaci, a few years later passed to the new University of Rome "Tor Vergata", becoming also Rector. The other four professor (Orsi, Filadoro, Pezzi, del Piano) continued their teaching in the successive years, with the collaboration of several associate professors, whose status was created by the law 382 in 1980. A later law on the short degree course required also the official participation of many researchers to the new teaching. Finally in 2001 the official activity of the Institute of Microbiology ceased and was incorporated in the Department of Public Health Sciences.

Cytokine networks and the regulation of uterine function in pregnancy and parturition.

Complex cytokine networks play an important role in a wide range of reproductive and pregnancy related processes. Here, we review the current knowledge concerning the impact of cytokines on uterine physiology and pathophysiology. Cytokines influence a range of uterine functions during the menstrual cycle, implantation, pregnancy and labour. The synergistic interactions between individual cytokines are intricate and dynamic, and modulated by pregnancy hormones. It is not surprising therefore, that perturbations to cytokine signalling are associated with adverse pregnancy outcomes, such as miscarriage, pre-eclampsia, preterm labour and foetal brain injury. Further insight into the complexity of cytokine networks will be required to develop novel therapeutic strategies for the treatment of cytokine imbalances in pregnancy.

Host inflammatory response profiling in preeclampsia using an in vitro whole blood stimulation model.

The pathophysiology of preeclampsia (PET) implicates an inflammatory dysfunction. This study profiled this host response by challenging whole blood with lipopolysaccharide. Multiplex immunoassays determined interleukin (IL)-1beta, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12(p70), IL-13, IL-17, granulocyte/granulocyte macrophage-colony stimulating factors (G-CSF/GM-SCF), interferon(IFN)-gamma, monocyte chemotactic protein (MCP)-1, macrophage inflammatory protein-1beta and tumor necrosis factor (TNF)-alpha levels. Secretory capacity was expressed in pg/million white cells or monocytes (+/-SEM). PET featured significantly higher IL-1beta, IL-2, IL-10, IL-13, G-CSF, IFN-gamma, MCP-1 and TNF-alpha monocyte secretory capacities (p < 0.05). The PET group exhibited an inflammatory hyper-responsiveness (p < 0.01) which was poorly described by the traditional Th1:Th2 dichotomy.

Lack of interleukin-4 receptor alpha chain-dependent signalling promotes azoxymethane-induced colorectal aberrant crypt focus formation in Balb/c mice.

Interleukin (IL)-4 receptor (IL-4R) alpha chain-dependent signalling by IL-4 and IL-13 promotes tumour growth and metastasis in mouse models of colorectal cancer. However, the role of IL-4R alpha-dependent signalling during the early, pre-malignant stages of colorectal carcinogenesis has not been investigated. Therefore, we investigated the effect of deletion of the IL-4R alpha gene on azoxymethane-induced colorectal aberrant crypt focus (ACF) multiplicity and size in Balb/c mice. IL-4R alpha(-/-) mice developed significantly more ACFs [median 8, inter-quartile range (IQR) 4-11.5; n = 9] than wild-type (WT) animals (median 4, IQR 1-6; n = 9; p = 0.04, Mann-Whitney U-test). There were significantly higher levels of IL-4 in serum from azoxymethane- and sham-treated IL-4R alpha(-/-) mice than WT animals, but no difference in serum IL-13 levels. In the absence of functional IL-4Rs, IL-13 can also signal via the IL-13R alpha2 receptor, leading to induction of transforming growth factor (TGF) beta, which has pro-tumourigenic activity at early stages of intestinal tumourigenesis. We found that mucosal TGFbeta mRNA levels and intestinal epithelial cell TGFbeta immunoreactivity were significantly higher in IL-4R alpha(-/-) mice than in WT animals. In summary, IL-4R alpha-dependent signalling has a protective, anti-neoplastic role during the post-initiation phase of azoxymethane-induced colorectal carcinogenesis in Balb/c mice. Our data should prompt thorough investigation of the role of IL-4R alpha-dependent signalling during human colorectal carcinogenesis, particularly as antagonism of IL-4R signalling represents a therapeutic strategy for asthma and other allergic diseases.

Randomized clinical trial of the effects of methylprednisolone on renal function after major vascular surgery.

BACKGROUND: Perioperative renal dysfunction following abdominal aortic aneurysm (AAA) repair is multifactorial and may involve hypotension, hypoxia and ischaemia-reperfusion injury. Studies of cardiac and hepatic transplant surgery have demonstrated beneficial effects on renal function of high-dose methylprednisolone administered before surgery. METHODS: Twenty patients undergoing elective open AAA repair were randomized to receive either methylprednisolone 10 mg/kg or dextrose (control) before induction of anaesthesia. Blood was analysed for a panel of cytokines representative of T helper cell type 1 and 2 subsets. Urine was analysed for subclinical markers of renal dysfunction (albumin, alpha(1)-microglobulin and N-acetyl-beta-D-glucosaminidase). RESULTS: Data from 18 patients were analysed. Both groups demonstrated glomerular and proximal convoluted tubular dysfunction that was unaffected by steroid treatment. Steroid administration increased serum levels of urea and creatinine (both P < 0.001). The steroid group had increased interleukin 10 levels (P = 0.005 compared to controls). There were no differences between groups in overall surgical complications, length of intensive care unit (P = 0.821) and hospital (P = 0.719) stay, or 30-day mortality. CONCLUSION: Methylprednisolone administration altered the cytokine profile favourably but adversely affected postoperative renal function.

An overview of cytokine interactions in atherosclerosis and implications for peripheral arterial disease.

Over the last three decades, a surge in research into the inflammatory pathophysiology of atherosclerosis has highlighted an array of cytokines and other inflammatory mediators associated with underlying inflammatory burden. The ability to identify and simultaneously measure multiple cytokines in peripheral blood highlights their potential as biomarkers of atherosclerosis. This has prompted much research in vascular medicine to identify the ;at-risk' groups for atherostenotic or atheroaneurysmal disease. This review is compiled with similar intentions and aims to discern the relevant evidence for cytokine profiling in peripheral arterial disease (PAD), where such information is lacking, while providing a holistic overview of cytokine interactions in atherosclerosis. This is pertinent given that cytokine profiles from coronary artery disease and aortic aneurysm studies cannot be directly extrapolated to PAD due to differences in inflammatory environments that exist in these conditions. Whilst plaque morphology and blood rheology play an important role in the cardiac manifestations of atherosclerosis, tissue thrombogenecity is very important in PAD. Further, cytokines act in concert rather than in isolation in a disease process, and no single cytokine in a cross-sectional model is able to serve as an absolute screening marker. Thus, it is essential to understand the regulation of cytokine production in atherosclerosis prior to evaluating the viability and merits of a multimarker approach for clinical risk stratification in PAD.

Human menopausal and pregnant mare serum gonadotrophins in murine superovulation regimens for transgenic applications.

Superovulation is a fundamental procedure for generating transgenic rodents. While various methods exist, zygote yield/quality remain suboptimal, making these techniques open to refinement. All require a follicle stimulating and a luteinising effect. The former can be induced by pregnant mare serum gonadotrophin (PMSG) or other compounds like human menopausal gonadotrophin (HMG). While HMG can double zygote yield compared to PMSG, no study has compared their effects on embryo quality. Embryo yield could also be increased with PMSG: timing administration at estrus may further improve follicular recruitment. This study compared: (i) the efficacy of HMG/PMSG for producing viable embryos for microinjection; and (ii) the effect of HMG/PMSG administration at estrus on embryo yield. Whitten effect-induced estrous C57/Bl6xCBA F(1) hybrid mice were superovulated as follows: PMSG (day 1; 5 IU intraperitoneally) or HMG (days 1 and 2; 1 IU intramuscularly); all received human chorionic gonadotrophin (hCG) on day 3 (5 IU, intraperitoneally). Zygotes were retrieved following mating, morphologically assessed and microinjected with innocuous ZhAT1R construct (expressing LacZ reporter and human angiotensin II type 1 receptor) before transfer to pseudopregnant recipients. Pups were tested for the transgene by Southern blot. Neither HMG nor PMSG proved superior in improving embryo yield, morphology and short-term post-microinjection survival. However, HMG group micromanipulated embryos all failed to establish a pregnancy/generate transgenic pups, unlike their PMSG counterparts. While HMG can be used for superovulation, it appears to increase embryo vulnerability to the long-term effects of microinjection. Furthermore, the embryo yields associated with HMG can be replicated by timing PMSG injection to coincide with Whitten effect-induced estrus.

Murine serum cytokines throughout the estrous cycle, pregnancy and post partum period.

Cytokines are pleiotropic glycoproteins participating in many aspects of mammalian reproductive physiology. Although murine models have been established to study normal and pathological pregnancy, the small volume of retrievable sample has hampered investigations into the role of cytokines in these processes. These problems were overcome by using fluid-phase multiplex immunoassays to monitor the serum profiles of 18 cytokines in single animals throughout normal murine reproduction: estrus, diestrus, post coitum, preimplantation, implantation, mid-pregnancy, late pregnancy and post partum. Most cytokines were detectable throughout all stages studied. Modest changes in profile were associated with estrous cyclicity and early pregnancy while virtually all cytokine levels increased markedly in mid- to late pregnancy and either fell slightly or levelled off post partum. The functional interrelationships between the various cytokines and the hormonal milieu are discussed with respect to gestational stage. Although certain profiles supported the 'conventional' Th1:Th2 cytokine paradigm of pregnancy, many of the changes recorded were orchestrated around IL-12 (p40) and (p70). The present findings suggest that the traditional cytokine dichotomy poorly describes complex immunological processes like pregnancy.

Rearrangement patterns of JC virus noncoding control region from different biological samples.

The JC virus (JCV) is generally considered the etiological agent of progressive multifocal leukoencephalopathy (PML), a demyelinating brain illness, often associated with immunosuppression and significantly frequent in acquired immunodeficiency syndrome (AIDS) patients. The primary infection by JCV is usually asymptomatic and the virus can remain in a latent status in the kidney. As a consequence of immunological alterations of the host, the virus can show a genetic variability in the noncoding control region (NCCR) due to deletions, duplications, and insertions as compared with the archetype. The NCCR of the archetype strain can be divided into six regions, named boxes A to F. In this study, the authors evaluated the presence of the JCV genome in different biological samples, such as urine, peripheral blood mononuclear cells (PBMCs) and cerebral spinal fluid (CSF) by means of polymerase chain reaction (PCR). After sequencing of the PCR fragments, the NCCR structure of isolated JCV strains was analyzed in order to verify the presence of different viral variants. An analysis of the homology and of the multiple alignment of the obtained sequences in comparison with the archetype strain has been carried out. The results indicated the presence of different rearrangements among the analyzed samples. Whereas in the urine, the NCCR structure always appeared very similar to that of the archetype, in the PBMCs and CSF, the NCCR sequences showed specific and characteristic rearrangements as compared to the archetype. These different rearrangements could be correlated with the emerging of an NCCR organization more suitable for the development of PML.

Detection and sequence analysis of human polyomaviruses DNA from autoptic samples of HIV-1 positive and negative subjects.

The distribution of DNA of BK and JC human polyomaviruses (BKV and JCV) was investigated in samples from autopsies of different organs in 2 groups of patients: Human Immunodeficiency Virus -1 (HIV) positive and negative. Samples from various organs were analysed by a nested polymerase chain reaction (PCR) for the non-coding control and for the VP1 regions of both viruses. The results obtained showed that BKV DNA was present in both males and females with a higher prevalence in HIV-positive subject samples (spleen: 33%; kidney: 44%; brain: 22%, uterine cervix:100%; prostatic urethra: 50%). In prostatic urethra samples of HIV-positive subjects, the JCV DNA was revealed in a low percentage (33%), while it was not found at all in uterine cervix samples of both groups. The varying presence of BK and JC viral DNA in the different organs seems to reflect the different pathogenetic attitude of these viruses. JCV was mainly present in the brain (55%), confirming its typical neurotropism and its etiological role in neurological disorders found in immunodeficient patients. BKV, on the other hand, was mainly present in the kidney (44%) and in genital organs (uterine cervix: 100%; prostatic urethra: 50%) with the latter finding favouring the hypothesis of a possible sexual transmission of BKV. Furthermore, our results confirm the crucial role of the immune system in the persistence of human polyomaviruses in the host.

Protection against reactive oxygen species during mouse preimplantation embryo development: role of EDTA, oxygen tension, catalase, superoxide dismutase and pyruvate.

Oxidative damage due to the production of reactive oxygen species (ROS) is one of a number of culture-induced stresses which may compromise preimplantation embryo development in vitro. Ethylenediaminetetraacetic acid (EDTA), reduced oxygen tension, superoxide dismutase (SOD) and catalase (CAT) offer protection against oxidative stress, but few attempts have been made to determine which of these agents, or which combination, is the most effective. In particular, no systematic investigation of their actions and interactions has been made using a multifactorial experimental design. Murine zygotes were cultured in the presence or absence of 10 miccroM EDTA, SOD (100-7,000 U/ml) and CAT (50-100 U/ml) at atmospheric (20%) and reduced (5%) oxygen tensions. Blastocyst formation and hatching rates (at various time points), and cell numbers were recorded, whilst parallel groups of embryos had their consumption of pyruvate, a hydrogen peroxide scavenger, measured. All parameters interacted significantly and affected blastocyst formation, hatching rate and cell numbers but the effect of EDTA was the most pronounced. There were beneficial effects of 5% O2, CAT and SOD, while 20% O2 had a deleterious effect on development. EDTA improved blastocyst formation and hatching rates but paradoxically led to a reduction in cell number. 5% O2 was the next most significant parameter to enhance embryo development and also increased cell numbers. No differences in pyruvate uptake were apparent between the various treatment groups. The results suggest that embryo culture in EDTA-free medium under 5% O2 provides the most practical and physiological conditions for in vitro murine embryo culture.

Pseudobactin biogenesis in the plant growth-promoting rhizobacterium Pseudomonas strain B10: identification and functional analysis of the L-ornithine N(5)-oxygenase (psbA) gene.

Pseudobactin(B10), the fluorescent siderophore produced by the rhizobacterium Pseudomonas strain B10, contains the hydroxamate ligand D-N(5)-hydroxyornithine (D-N(5)-OH-Orn). We cloned the L-Orn N(5)-oxygenase (psbA) gene from a genomic library of Pseudomonas strain B10 and demonstrated that PsbA is involved in the conversion of L-Orn to its N(5)-OH derivative. PsbA shows significant similarity to microbial omega-amino acid hydroxylases containing flavin adenine dinucleotide and NADP cofactor-binding sites and the FATGY signature of the putative substrate recognition pocket. The psbA gene is monocistronic, and its transcription is negatively controlled by iron. A site-specific psbA mutant of Pseudomonas strain B10 was biochemically complemented with the precursor L-N(5)-OH-Orn, suggesting that L-Orn is hydroxylated before conversion to the D isomer. The L-Orn N(5)-hydroxylase-defective mutants of Pseudomonas strain B10 and Pseudomonas aeruginosa PAO1 were much less effective than the parental strains in suppressing the growth of the phytopathogen Erwinia carotovora in iron-poor medium. The extent of in vitro inhibition of E. carotovora was strictly iron dependent and directly correlated with the amount of released siderophores. These data strengthen the role of fluorescent siderophores in biocontrol of deleterious rhizomicroorganisms.

Metal complexes of lactoferrin and their effect on the intracellular multiplication of Legionella pneumophila.

The action of bovine lactoferrin saturated with iron, zinc and manganese on the intracellular multiplication of Legionella pneumophila in HeLa cells has been tested. The results obtained showed that lactoferrin did not influence the invasive efficiency of Legionella. The intracellular multiplication of the bacterium was inhibited by apo-lactoferrin and by lactoferrin saturated with manganese and zinc, whereas lactoferrin saturated with iron enhanced the intracellular growth. Experiments in parallel were performed with iron, manganese and zinc citrate to test the effect due to the metal ions alone. Even in this condition the addition of an iron chelate enhanced the multiplication of Legionella while the manganese chelate produced a certain inhibition.