BDNF Val66Met polymorphism and brain volumes in multiple sclerosis.

Brain derived neurotrophic factor (BDNF) regulates several CNS physiological and pathological processes. To investigate in multiple sclerosis (MS) patients, the relationship between the Val66Met polymorphism of BDNF and clinical markers of disease activity and MRI markers of focal and diffuse brain pathologies. 45 MS patients and 34 healthy controls (HCs) were genotyped and subjected to clinical-MRI examination. Global white matter fraction (gWM-f), gray matter-f (GM-f), cerebrospinal fluid-f (CSF-f), and abnormal WM-f were measured. We studied 26 Val/Val and 19 Val/Met patients and 23 Val/Val and 11 Val/Met HCs. We found that Val/Val patients had lower GM-f and higher CSF-f than Val/Val HCs; such differences were not statistically significant comparing Val/Met patients to HCs. The regression analysis showed that both Val/Met genotype and relapse number were associated with lower CSF-f. Our data suggest that Met allele might be a protective factor against MS as it is associated to a lower brain atrophy.

Identification of IP-10 and IL-5 as proteins differentially expressed in human complicated and uncomplicated carotid atherosclerotic plaques.

Inflammation plays a crucial role in the development and progression of atherosclerotic plaques. The aim of this study is to compare culture supernatants from uncomplicated and complicated carotid atherosclerotic plaques by a multiplex approach, to assess the molecular mediators associated with a plaque complicated phenotype. Atherosclerotic plaques were obtained from 17 patients undergoing carotid endarterectomy. Supernatants from plaque cultures were evaluated by Bio-Plex cytokine assay to determine 27 pro- and anti-inflammatory cytokines, chemokines and growth factors. Complicated plaques secreted higher levels of IP-10 (p = 0.027) and lower levels of IL-5 (p = 0.045) than did uncomplicated ones. Distinctive secretory patterns of cytokines, chemokines and growth factors were present in the two types of plaque. Our study identifies IP-10 and IL-5 as proteins differentiating complicated and uncomplicated plaques from human carotid arteries and provides new insights into the interplay of molecular mediators with atherosclerotic plaque progression.

The effect of azidothymidine on germ tube formation in Candida albicans.

Candida albicans have a marked propensity to cause infections in AIDS patients. A virulent trait of C. albicans is the yeast-hypha transition (Y-->H) which is influenced, in vitro and in vivo, by several factors. Since azidothymidine (AZT) is used in HIV-positive patients, the effect, in vitro, of different concentrations of AZT on C. albicans Y-->H transition was evaluated. C. albicans isolated from HIV-negative and HIV-positive patients were used and strains of C. tropicalis isolated from HIV-positive patients were also tested. AZT concentrations from 0.01 microg/ml to 10 microg/ml did not have any influence on the Y-->H transition, whereas 100 microg/ml AZT significantly inhibited the germ tube formation. AZT did not influence the formation of pseudohyphae in C. tropicalis. It is suggested that C. albicans infection observed in HIV-positive patients was not influenced by AZT therapy, because at currently used dosages, the Y-->H transition was not expected to increase.

Epidemiological trend of human leptospirosis in Italy between 1994 and 1996.

In the three-year period 1994 1996, 222 reports on human cases of leptospirosis were received by the Italian Ministry of Health. The average annual number of reports was 29.2% lower than in the preceding eight years. In all cases but two the infections were thought to have been acquired in Italy. As in previous years, the majority of cases was observed in the northern regions of the country (83.8%), mostly in males (88.9%). Cases occurred in all age groups, but were more common in the working-age population (15-64 years). There was no common-source outbreaks. The typical leptospiral seasonal course, with a peak in August, was observed. During 1994, leptospirosis was the reported cause of death in 19 patients. Mortality was higher among males than females. The overall fatality rate was 22.6%. During the study period, a total of 126 cases of leptospirosis were confirmed by the National Centre for Leptospirosis or one of the 12 Regional Leptospira Laboratories. Of the 103 patients for whom information on place of residence, contact with animals, occupational and recreational activities was available, 98 (95.1%) were people who live in rural areas or devote themselves to occupational or recreational activities at risk. The likely source of infection and the mode of exposure were known for 55 patients. Forty-five patients (81.8%) were likely infected by contaminating water (43 cases) or soil (2 cases), ten (18.2%) by direct contact with animals or animal urine. Both running (51.2%) and stagnant water (27.9%) have been reported as a source of infection. Rodents were implicated in 50.0% of the 10 cases involving animals. In comparison with the preceding eight-year period, the risk of contracting leptospirosis was found to have increased for recreational activities (from 34.7 to 38.2%) and decreased for occupational activities (from 45.8 to 32.7%). A large number of infections, however, was ascribed to accidental events (25.5%). As in the previous period, besides fever, the involvement of the liver was the most frequent clinical manifestation (70.8%). Influenza-like symptoms were the only signs of illness in 15.1% of cases. Infections by 9 different serogroups were detected. The most frequent antibodies were those against serovars icterohaemorrhagiae, poi, copenhageni and brattislava. The presence of co-agglutinins against serovars belonging to different serogroups prevented the identification of the presumptive infecting serogroup in 19.8% of subjects.

Evaluation of nonspecific immunity and plasma levels of interferon-gamma, interleukin-6 and tumor necrosis factor-alpha in preeclampsia.

In this study we evaluated the maternal cell-mediated immune aspects of preeclampsia in terms of phagocytosis and killing of monocytes and polymorphonuclear cells. To evaluate the contribution of cytokines (Cks) in the pathophysiology of preeclampsia, we investigated the plasma levels of interferon-gamma (IFN-gamma), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha), respectively, by an enzyme-linked immunosorbent assay. Data showed that phagocytic and killing activities of monocytes were depressed in preeclamptic and normal pregnancies. At the same time, IFN-gamma plasma levels were undectable in both groups. Conversely, we detected significant levels of TNF-alpha in plasma from preeclamptic and normal pregnancies. Moreover, since in three preeclamptic patients the onset of severe preeclampsia was associated with a sharp increased of TNF-alpha plasma levels, we suggest that an increased production of this CK may be implicated in the pathophysiology of preeclampsia.

Antibodies to Chlamydia pneumoniae in healthy children from Bari, south Italy.

Specific IgG and IgM antibodies to Chlamydia pneumoniae were evaluated by microimmunofluorescence test in a group of healthy subjects (age 0-18 years). Antibody titers (IgG) > or = 1:16 were found in 9.7% of the age group 0-1 years, in 5.3% of the group of 2-3 years and rose to 19% in children of the group 4-6 years. The seroprevalence was 11% and 17.1% in the group 7-12 years and 13-15 years, respectively. In the last group of 16-18 years the seroprevalence was 9.1%. The overall seroprevalence was 11.8% and C. pneumoniae infection is acquired before school age. In addition, in our pediatric patients it seems that C. pneumoniae does not play an important pathogenic role, being responsible for only 1.6% of the acute lower respiratory infections. The factors that may account for these findings are discussed.

In vitro antimicrobial properties of azidothymidine (AZT).

In addition to the activity against a number of retroviruses, azidothymidine (AZT) has antibacterial activity against many bacteria. The effect of AZT on 224 bacterial species, including 25 strains of Salmonella spp. isolated from HIV-positive patients, was tested. AZT had no activity against all the strains of tested Gram-positive bacteria and Pseudomonas species (MIC > 128 micrograms/ml), whereas a different activity against Enterobacteriaceae (MIC range, 128 to 0.06 micrograms/ml) was found. In particular 76% of Salmonella spp. isolated from HIV-positive patients showed MICs > 1 microgram/ml, whereas similar MICs value were found in 50% of the Salmonella strains isolated from HIV-negative subjects. In addition, strains of Salmonella isolated from stools were more resistant to AZT when compared to strains isolated from blood even if this difference was not statistically significant. No correlation was found between length of therapy and Salmonella resistance to AZT in HIV-positive patients and a low incidence of Salmonella relapses in subjects treated with AZT was observed. The possibility that AZT may have an ancillary benefit in controlling some bacterial infections in AIDS patients is discussed.

Polarizing response of human polymorphonuclear cells to Vibrio cholerae.

Leucocytes have the capacity to respond to chemotactic factors by becoming morphologically and functionally polarized and this method has been found to be suitable for measurement of chemotaxis. This work evaluates the effect of whole Vibrio cholerae biotype El Tor polarization of human polymorphonuclear (PMN) cells in comparison with strains of V. cholerae NAG, Vibrio alginolyticus and Salmonella typhi. V. cholerae O1 induced, at different cell/bacteria ratios, a significant increase in the percentage of polarized cells compared with PMN cells stimulated with formylmethionyl-leucyl-phenylalanine (FMLP) and the other bacteria tested. The capacity of V. cholerae O1 to induce PMN cell polarization may play a role on the inflammatory response recently described in diarrhoea caused by V. cholerae.

Spontaneous binding of Vibrio cholerae to human leucocytes.

Various lymphocyte subpopulations have the capacity to bind different strains of Gram-negative bacteria. The capacity of a strain of Vibrio cholerae, biotype El Tor, isolated during an outbreak of cholera, to adhere to mononuclear cells isolated from peripheral blood was evaluated. V. cholerae binds to mononuclear cells in a dose-dependent manner. The binding was 76.1% at a cells/bacteria ratio of 1:200 and significantly decreased to 43.1% at a ratio of 1:1. The value of bound bacteria, a marker of the mean number of binding sites on the cell surface, decreased at lower cell/bacteria ratios. Studies on isolated cellular populations demonstrated that 51, 42 and 38%, respectively, of CD4+, CD8+ and B cells were bound by V. cholerae whereas monocytes exhibited a higher binding capacity. The data suggest that the percentage binding of V. cholerae to lymphocytes and monocytes was higher than the percentage found in previous studies with Gram-negative bacteria such as Yersinia enterocolitica, and Salmonella, but similar to Helicobacter pylori. The findings indicate that V. cholerae possesses multiple 'adhesins' such as fimbriae, flagella, haemagglutinins, lipopolysaccharides, and outer membrane proteins. The capacity to bind to blood lymphocytes may reflect the same capacity for the lymphocytes from the gastrointestinal associated lymphoid tissue. This cytoadherence may contribute to the uptake of V. cholerae from the gut and may contribute to activation of B cells and CD4+ lymphocytes.

Human leptospirosis in Italy, 1986-1993.

In the eight-year period 1986-1993, the Italian National Center for Leptospirosis and the Regional Leptospira Laboratories confirmed 312 cases of clinical leptospirosis by using the microscopic agglutination (MA) assay. The majority of cases was observed in Northern regions of the Country. Cases were reported in all age groups, but were most common in the working-age population. Of 312 cases, 291 (93.3%) occurred among males. The largest number of infections was ascribed to occupational activities (45.8%). The typical leptospiral seasonal course, with a peak during the summer, was observed. Involvement of the liver was the most frequent manifestation. Influenza-like symptoms were the only signs of illness in 11.1% of cases. Anti-leptospira antibodies, cross-reacting with two or more serovars, were found in 28.2% of sera. The most frequent serovar-specific antibodies were those against poi, icterohaemorrhagiae, bratislava, copenhageni and sejroe.

[Anti-Legionella pneumophila antibody titers in blood from children and adults with lung diseases of unknown etiology]. / Titoli anticorpali anti-Legionella pneumophila in sieri di bambini ed adulti con pneumopatie ad eziologia sconosciuta.

175 sera from children and 101 sera from adults both with respiratory illness of unknown origin were collected between September 1980 and February 1983 and studied by using the indirect immunofluorescence test for Legionnaires' disease. By using the criteria of the Center for Disease Control for a positive (fourfold increase in titer over 128 during convalescence) or presumptive (single titer greater than or equal to 256) serological test, 8 samples from adults (7.92%) and 11 samples from children (6.27%) gave a positive result. These results suggest that the frequency of Legionnaires' disease is similar in both adults and children.

Legionella pneumophila and related organisms induce the generation of procoagulant activity by peripheral mononuclear cells in vitro.

We investigated the in vitro effect of various members of the genus Legionella on human peripheral mononuclear cells. All the strains tested induced the generation of strong procoagulant activity (tissue factor) when incubated for a prolonged period of time with pure mononuclear cell suspensions. This effect was dependent on the number of bacteria. The production of mononuclear cell procoagulant activity was also observed after the addition of bacteria to citrated whole blood. Escherichia coli 0111:B4 showed similar activity, but Staphylococcus aureus was much less effective. These findings suggest that the presence of endotoxin-like substance(s) in the outer cell wall of Legionellae could contribute to the stimulation of mononuclear cells. The production of tissue factor, a potent trigger of blood clotting, by these cells could help us to understand the mechanism(s) responsible for the activation of intravascular coagulation associated with severe legionellosis.

Legionellosis in an infant: first case in Italy.

Among several children admitted in Hospital with febrile acute pneumonia, it has been found - by indirect immunofluorescence assay a significant seroconversion for Legionella pneumophila serogroup 1, compatible with a recent infection, in an 18-month-old boy. The clinical course of the disease was favourable, and a prompt recovery as observed after administration of an antibiotic (cefuroxime) stable to the bacterial beta-lactamase.