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Biomedical subjects

A D'Alessandro

Publications and source records attributed to A D'Alessandro.

At least 37 records · Page 2Linked to original sources

Early pulmonary cytokine responses to zinc oxide fume inhalation.

Zinc oxide inhalation causes metal fume fever, a flu-like syndrome common among welders. Proinflammatory pulmonary cytokines play a role in mediating this occupational illness. The goal of this investigation was to characterize early pulmonary cytokine responses after experimental human exposure to inhaled purified zinc oxide fume. We quantified bronchoalveolar lavage (BAL) cytokine concentrations in 15 healthy volunteers 3 hr after inhalation of zinc oxide fume. We compared postexposure cytokine responses with postsham exposure responses in the same 15 subjects. We also compared cytokine responses with those of 14 "late follow-up" subjects previously studied by BAL 20 hr after zinc oxide fume exposure. Zinc oxide exposure was a statistically significant, dose-dependent predictor of increases in BAL TNF (mean exposure-sham difference +/- SE = 9.5 +/- 3.6 pg/mL, P = 0.02), IL-6 (mean exposure-sham difference +/- SE = 5.5 +/- 1.8 pg/mL, P = 0.009), and IL-8 (mean exposure-sham difference +/- SE = 64.1 +/- 23.9 pg/mL, P = 0.02). The TNF response was significantly greater at 3 hr follow-up compared with 20 hr follow-up, after adjusting for smoking status, zinc dose, and BAL macrophages (P = 0.004). Our findings provide evidence for a pulmonary inflammatory response 3 hr after inhalation of zinc oxide fume characterized by dose-dependent increases in BAL proinflammatory cytokine concentrations. These data indicate that TNF plays an important initial role in mediating metal fume fever.

Adult↗

Some effects of adding p-LH in defined amounts to purified p-FSH to modify FSH/LH ratios during the superovulatory treatment of anestrous ewes.

Nonlactating Leccese ewes (n = 61) were used during seasonal anestrus to investigate the effects on ovarian response and embryo production of adding defined amounts of p-LH to purified p-FSH as well as decreasing the FSH/LH ratio during treatment. The ewes were synchronized with FGA-impregnated intravaginal pessaries for 9 days and prostaglandin F2 alpha (Cloprostenol) injected on the seventh day. They were divided into six treatment groups in a 3 x 2 factorial design: three amounts of purified p-LH (100, 50 or 25% equivalent to 525, 262 or 131 IU p-LH) x 2 regimen of p-FSH and p-LH administration (constant or decreasing FSH/LH ratio). Each ewe received a total of 525 IU p-FSH at a decreasing dose, twice daily over a 3-day period. Group I (n = 11), Group II (n = 10) and Group III (n = 10) were treated with p-FSH supplemented with p-LH at 100%, 50% and 25%, respectively, of p-FSH dose and a constant FSH/LH ratio throughout the treatment period. Group IV (n = 10), Group V (n = 10) and Group VI (n = 10) were treated with p-FSH supplemented with p-LH at 100%, 50% and 25%, respectively, of p-FSH dose but with a decreasing FSH/LH ratio over the 3 days of the treatment: 1.7-0.86-0.43 for Group IV; 3.4-1.7-0.86 for Group V; 6-3-1.5 for Group VI. Embryos were flushed surgically on Day 6 after estrus. The ovulation rate did not differ among the groups (8-12.8). Superovulation with 100% p-LH and decreasing the FSH/LH ratio (Group IV) resulted in: (i) the highest ova recovery (9.8 +/- 1.7), and this was significantly different (P < 0.05) from the 25% p-LH treated group (Group VI; 5.0 +/- 1.7), (ii) the highest fertilization rate (90.6 +/- 9.2%), with a significant (P < 0.01) difference compared with the constant ratio regimen (Group I; 62.6 +/- 8.3%); (iii) the highest transferable embryo yield (6.4 +/- 1.1), differing significantly (P < 0.01) from Group VI (2.2 +/- 1.1) and Group I (2.7 +/- 1.0). It is concluded that decreasing the amount of p-LH added to purified p-FSH did not improve the superovulatory response of ewes during the anestrous period. Transferable embryo production was significantly improved when ewes were treated with p-LH equivalent to 100% p-FSH, with the FSH/LH ratio decreasing during treatment.

Anestrus↗

Pulmonary responses after wood chip mulch exposure.

Organic Dust Toxic Syndrome (ODTS) is a flu-like syndrome that can occur after inhalation of cotton, grain, wood chip dusts, or other organic dusts or aerosols. We investigated whether inflammatory pulmonary responses occur, even after relatively brief, low-level wood chip mulch exposure. Six volunteers were exposed to wood chip mulch dust. Total dust and/or endotoxin levels were measured in five subjects. Pulmonary function and peripheral blood counts were measured before and after exposure in each subject. Bronchoalveolar lavage (BAL) was performed in each subject after exposure, and cell, cytokine, and protein concentrations were measured. Control BAL without previous exposure was also performed on three of the subjects. Three of six subjects had symptoms consistent with ODTS. No clinically relevant or statistically significant changes in pulmonary function tests after exposure were found. Three subjects manifested a marked elevation in neutrophil percentage in their BAL (range, 10 to 57%). When these three subjects underwent control BAL, the postexposure comparison demonstrated an increase in neutrophil levels of 154 +/- 89 x 10(3)/mL (mean +/- standard error; P = 0.22). The mean increase in BAL interleukin-8 levels after exposure, compared with paired control values, was 11.2 +/- SE 2.5 pg/mL (P = 0.047). There was also an increase in BAL interleukin-6 levels that reached borderline significance (6.4 +/- SE 2.0 pg/mL; P = 0.08). Tumor necrosis factor levels were increased in all three subjects' BAL as well (0.4 +/- SE 0.2 pg/mL), but this change was not statistically significant (P = 0.2). Our findings of increased BAL proinflammatory cytokine and neutrophil levels are consistent with the theory that cytokine networking in the lung may mediate ODTS.

Adult↗

Human pulmonary responses to experimental inhalation of high concentration fine and ultrafine magnesium oxide particles.

Exposure to air polluted with particles less than 2.5 micron in size is associated epidemiologically with adverse cardiopulmonary health consequences in humans. The goal of this study was to characterize human pulmonary responses to controlled experimental high-dose exposure to fine and ultrafine magnesium oxide particles. We quantified bronchoalveolar lavage (BAL) cell and cytokine concentrations, pulmonary function, and peripheral blood neutrophil concentrations in six healthy volunteers 18 to 20 hr after inhalation of fine and ultrafine magnesium oxide particles produced from a furnace system model. We compared postexposure studies with control studies from the same six subjects. Mean +/- standard deviation (SD) cumulative magnesium dose was 4,138 +/- 2,163 min x mg/m3. By weight, 28% of fume particles were ultrafine (<0.1 micron in diameter) and over 98% of fume particles were fine (<2.5 micron in diameter). There were no significant differences in BAL inflammatory cell concentrations, BAL interleukin (IL)-1, IL-6, IL-8, tumor necrosis factor, pulmonary function, or peripheral blood neutrophil concentrations postexposure compared with control. Our findings suggest that high-dose fine and ultrafine magnesium oxide particle exposure does not produce a measurable pulmonary inflammatory response. These findings are in marked contrast with the well-described pulmonary inflammatory response following zinc oxide particle inhalation. We conclude that fine and ultrafine particle inhalation does not result in toxicity in a generic manner independent of particle composition. Our findings support the concept that particle chemical composition, in addition to particle size, is an important determinant of respiratory effects.

Adult↗

Serum concentrations of methanol after inhalation at 200 ppm.

Methanol has been proposed as an alternative automotive fuel to reduce pollution in the urban environment. Utilization of methanol will increase exposure to low levels of methanol vapors for the general public and in occupational settings. Information on absorption by inhalation and serum concentrations after low-level exposure would be important in evaluating the health impact of generalized methanol exposure. During a randomized double-blind study of the potential neurobehavioral effects of inhaled methanol at 200 ppm for 4 hours, 15 timed specimens from 22 subjects were obtained for methanol analysis by head-space gas chromatography. Methanol was rapidly absorbed by inhalation (absorption rate constant = 0.87 +/- 0.60 hours-1). Serum methanol concentrations were increased by more than fourfold at the end of the exposure period (6.5 +/- 2.7 vs 0.9 +/- 0.6 mg/L), as were urinary methanol excretion rates, although formate concentrations were not increased over background concentrations. The overall (n = 22) elimination half-life was 3.2 +/- 2.3 hours. Elimination from plasma fit a monoexponential model for only half of the subjects during the 4-hour postexposure follow-up period (mean half-life = 2.2 hours). Subjects with poor fits either showed greater variability or apparent slow (nonsignificant) declines in serum methanol concentrations, possibly because of the offsetting contributions of dietary intake or endogenous production, but more likely as a result of the limited number of sampling times and limited follow-up period.

Adult↗

Dose-dependent cigarette smoking-related inflammatory responses in healthy adults.

The aim of this study was to determine the dose-response relationship between cigarette smoke exposure and pulmonary cell and cytokine concentrations in bronchoalveolar lavage (BAL). BAL cells and BAL supernatant concentrations of tumour necrosis factor-alpha (TNF alpha), interleukin (IL)-1 beta, IL-6, IL-8, and monocyte chemoattractant protein (MCP)-1 from 14 healthy smokers and 16 healthy nonsmokers were quantified. Statistically greater concentrations of neutrophils, macrophages, IL-1 beta, IL-6, IL-8 and MCP-1 were observed among smokers compared with nonsmokers (p < or = 0.0007 in all cases). Cigarette smoking, categorized ordinally as: less than one pack, one pack, or greater than one pack per day, was predictive of BAL macrophages (p < 0.0001), neutrophils (p = 0.015), IL-1 beta (p < 0.001) and IL-8 (p = 0.02). We conclude that concentrations of macrophages, neutrophils, IL-1 beta and IL-8 are elevated in the pulmonary microenvironment of smokers in a cigarette dose-dependent manner. Based on the present findings, we would caution against simple analyses that treat current smokers as a homogeneous group and which do not account for smoking intensity.

Adolescent↗

Exaggerated responses to chlorine inhalation among persons with nonspecific airway hyperreactivity.

Although chlorine gas is a common irritant exposure, little is known about airway responses to chlorine inhalation among persons with baseline airway hyperreactivity. We wished to determine whether such persons manifest an exaggerated response to chlorine compared with normal subjects. We studied 10 subjects, five with and five without airway hyperresponsiveness (HR) after exposure to 1.0 ppm chlorine and five persons, all with HR, to 0.4 ppm chlorine. After 1.0 ppm inhalation, there was a significant (p < 0.05) fall (mean +/- SE) in FEV1 immediately following exposure among normal (-180 +/- 37 mL) and HR subjects (-520 +/- 171 mL). The fall was greater among the HR compared with the normal subjects (p = 0.04). Specific airway resistance (Sraw) increased to a greater degree among the HR group compared with normal subjects (p = 0.04). Among all subjects (n = 10), the proportional change in FEV1 after 1.0 ppm chlorine correlated with baseline reactivity (Spearman rank correlation r = 0.64, p < 0.05). At 24-h follow-up, there were no significant chlorine-related pulmonary function deficits. After 0.4 ppm chlorine inhalation, there was no significant pulmonary function effect. These data indicated that persons with hyperreactive airways manifest an exaggerated airway response to chlorine at 1.0 ppm. This suggests that when large numbers of persons are exposed to chlorine, a susceptible subpopulation may acutely respond with a greater decrement in pulmonary function.

Adult↗

Epstein-Barr virus DNA is present both in CD10/CD77 positive and negative subsets of human tonsillar lymphocytes.

We report the fractionation of freshly isolated subsets of tonsillar lymphocytes according to cell density and double sorting for the differential expression of CD10 and CD77, and their analysis for the presence of Epstein Barr virus genome by nested PCR. All the subsets of tonsillar lymphocytes gave unequivocal evidence for the presence of EBV DNA, when obtained from EBV seropositive individuals. Confirmation of all cases examined demonstrates that B lymphocytes from the germinal centers of tonsils are also involved in carrying the EBV infection in vivo.

Adolescent↗

Neurobehavioral effects of low-level methanol vapor exposure in healthy human volunteers.

Methanol-powered vehicles are being introduced in the United States as a solution to air pollution. This study assessed whether acute exposure to methanol vapor at the current industrial threshold limit value of 200 ppm for 4 hr has adverse effects on human neurobehavioral performance. Twenty-six healthy subjects (15 men, 11 women; ages 26-51 years) were exposed to methanol or water vapor for 4 hr while seated in a chamber. The subjects served as their own controls in a randomized, double-blind study design. The variables assessed were serum and urine methanol and formate levels; visual performance (color discrimination and contrast sensitivity); and neurophysiological (auditory evoked potentials) and neurobehavioral performances. Exposure to methanol increased serum concentrations and urinary excretions of methanol, but did not affect formate levels. Overall visual, neurophysiological, and neurobehavioral test outcomes were not significantly affected, unless certain between-subject variables are considered. Slight effects on P-300 amplitude and Symbol Digit testing were noted. We conclude that acute exposure of healthy people to low concentrations of methanol had little effect on these measures of neurobehavioral performance.

Administration, Inhalation↗

Embryo production and endocrine response in ewes superovulated with PMSG, with or without monoclonal anti-PMSG administered at different times.

Mature nonlactating Altamurana ewes (n = 168) were synchronized in the seasonal anestrus period with FGA-impregnated intravaginal pessaries for 12 d. In Experiment 1, 48 ewes were divided into a 3 x 4 factorial design for anti-PMSG monoclonal antibody (AP) bioassay test. Concomitant injections of PMSG (1000, 1500, 2000 IU) and AP (0, 1, 2, 3 microl/IU PMSG) were given, and ovarian response was evaluated by laparoscopy. In Experiment 2, 120 ewes were divided into 8 experimental groups (n = 15 per group). The ewes treated with 1000 or 1500 IU PMSG at -24 h from sponge removal were given AP intravenously at 50 h after pessary withdrawal, 12 or 24 h after the onset of estrus, while the controls did not receive AP. Blood samples were collected from ewes (n = 6) treated with 1500 IU PMSG with or without anti-PMSG. Ovarian response and embryo production were evaluated on Day 7 after sponge removal upon laparotomy. It was found that 1 microl AP was effective in neutralizing 1 IU PMSG. No significant differences in serum concentrations of progesterone were observed among the groups of superovulated ewes. Estradiol-17 beta levels were reduced following AP treatment 12 h after the onset of estrus. At a lower dosage of superovulatory treatment (1000 IU PMSG), AP injected at 12 or 24 h after the onset of estrus significantly lowered large follicles (P < 0.01) and increased the rate of ovulation (P < 0.05). Moreover, embryo production showed a more than two-fold increase (P < 0.01) of viable embryos following AP injection at 12 or 24 h after the onset of estrus (3.2 to 3.3 vs 1.3, with vs without anti-PMSG). It is concluded that superovulatory treatment with 1000 IU PMSG plus AP administered at a fixed time after the onset of estrus may improve ovarian response and the yield of viable embryos in ewes.

Journal Article↗

Second recorded case of human infection by Echinococcus oligarthrus.

The paper reviews a previously published case of hydatid disease in the human heart of a Brazilian person who died of tetanus. Based on present knowledge about the distinguishing characteristics of Echinococcus granulosus, E. vogeli, and E. oligarthrus, it was recognized that the infection was due to E. oligarthrus, mainly based the morphologic features of the hooklets of the protoscolex. This is the second human infection due to E. oligarthrus and the first showing wall features of cysts. Therefore, some human infections of polycystic hydatid disease observed outside the range of the bush dog, the only definitive host of E. vogeli (Panama to Northern Argentina), may be due to E. oligarthrus rather than to E. vogeli.

Aged↗

Immunodiagnosis of polycystic hydatid disease/polycystic echinococcosis due to Echinococcus vogeli.

A crude antigenic metacestode extract from Echinococcus vogeli was assessed by enzyme-linked immunosorbent assay (ELISA) and showed strong binding activity with serum antibodies from patients with polycystic echinococcosis. Major cross-reactions occurred with serum antibodies from patients with cystic and alveolar echinococcosis and from patients infected with other species of helminths. An E. vogeli antigen fraction, Ev2, was subsequently purified by immunosorption. The respective Ev2 ELISA demonstrated improved specificity, allowing discrimination of non-Echinococcus infections from polycystic echinococcosis. Based upon the calculation of a comparative (Ev-crude ELISA versus Ev2 ELISA) reactivity index, it became possible to discriminate all cystic echinococcosis cases, but only some alveolar echinococcosis cases, from polycystic echinococcosis. Immunoblot analyses revealed an antibody banding pattern highly conserved among polycystic, cystic, and alveolar echinococcosis. However, immunoblotting reliably distinguished between echinococcosis and all non-Echinococcus infections.

Animals↗

Pulmonary responses to purified zinc oxide fume.

BACKGROUND: Metal fume fever is a flu-like illness caused by zinc oxide fume inhalation and mediated by unknown mechanisms. It is one of a group of work-related febrile inhalational syndromes. We studied bronchoalveolar lavage (BAL) obtained from cigarette smoking and nonsmoking human volunteers after controlled exposure to purified zinc oxide fume to explore the possible roles of proinflammatory cytokines in this condition. METHODS: We studied 14 volunteers after inhalation exposure to purified zinc oxide fume and after sham exposure to air. The mean cumulative exposure was 537 +/- 232 mg min per cubic meter elemental zinc. Twenty hours after exposure we performed BAL. We analyzed BAL cells and studied BAL supernatant for cytokines including tumor necrosis factor-alpha (TNF alpha), interleukin(IL)-8, and IL-1 by enzyme-linked immunosorbant assay (ELISA). RESULTS: Polymorphonuclear leukocytes (PMNs) were significantly increased in the BAL fluid obtained post-exposure compared to sham (mean difference = 41.3 +/- 16.8 x 10(3) per mL; p < 0.05). Cumulative zinc exposure positively correlated with exposure-sham differences in BAL supernatant concentrations of both TNF (r2 = 0.58; p = .002) and IL-8 (r2 = 0.44, p = 0.01). Exposure-sham concentration differences in BAL supernatant IL-8 and BAL PMNs were also positively correlated (r2 = 0.60; p < 0.001). Cigarette smoking was not associated with exposure-sham differences in BAL TNF or IL-8, but did demonstrate a packs-per-day dependent increase in BAL supernatant IL-1 (t = 2.3, p = 0.04) post-exposure compared to sham, after taking into account the zinc exposure response. CONCLUSIONS: Purified zinc oxide fume inhalation causes an exposure-dependent increase in proinflammatory cytokines and PMNs in the lung. This supports a role for cytokine networking in mediating metal fume fever.

Adult↗

Electrochemical determination of low blood lead concentrations with a disposable carbon microarray electrode.

Lead concentrations in blood samples typical of unexposed individuals are determined by using square-wave anodic stripping voltammetry at a disposable 287-element (15-35-microns diameter) carbon microarray electrode. Analysis of a series of low Pb-containing samples (blood [Pb] = 17 to 92 micrograms/L) by standard addition gives good accuracy (average bias vs graphite furnace atomic absorption spectroscopy = -4 micrograms/L) and precision (pooled SD = 7 micrograms/L). The signal/noise ratio is improved by about an order of magnitude over that found at a single carbon disk (10 microns diameter), resulting in a detection limit (for the microarray) of 5 micrograms/L for a 60-s deposition of sample.

Carbon↗

Determination of lead in blood by square wave anodic stripping voltammetry at a carbon disk ultramicroelectrode.

A method for blood lead ([Pb]) analysis is developed based on square wave anodic stripping voltammetry (SWASV) in an Hg(2+)-containing solution using a 10-microns-diameter carbon disk ultramicroelectrode. SWASV eliminates interference from O2 in unsparged blood-derived sample solutions, and filtration of acidified samples through nitrocellulose reduces the concentration of interfering substances, increasing the size and improving the uniformity of peak currents. Blood [Pb] values obtained by SWASV are compared with blood [Pb] values determined by graphite furnace atomic absorption spectrophotometry; good accuracy and reasonable coefficients of variation in the range 10.6-20% (average of 13.5%) are found for blood [Pb] ranging from 4 to 30 micrograms/dL. Preliminary experiments using a carbon disk microarray electrode suggest future improvements in sensitivity.

Electrochemistry↗