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Biomedical subjects

A D'Alessandro

Publications and source records attributed to A D'Alessandro.

At least 19 recordsLinked to original sources

Active immunization with a synthetic fragment of pig inhibin alpha-subunit increases ovulation rate and embryo production in superovulated ewes but season affects its efficiency.

Two experiments were designed to determine the effects of active immunization against one of two synthetic peptides from humans (inhibin-like peptide) or pigs (inhibin alpha-subunit) on antibody titres, ovulation rate and embryo production in ewes superovulated with 16 U ovine FSH. In Expt 1, during the breeding season, 30 ewes were subdivided into three groups: group I served as the non-immunized control; group II was immunized against inhibin-like peptide (100 micrograms inhibin-like peptide equivalent, followed by three booster injections); group III was immunized against pig inhibin alpha-subunit conjugated to human serum albumin (96 micrograms for the primary administration and 46 micrograms for the booster). In Expt 2, the efficiency of immunization against pig inhibin alpha-subunit on ovarian response and embryo production was evaluated during the non-breeding season in two groups of ewes (n = 12): group IV was a non-immunized control; Group V was immunized against pig inhibin alpha-subunit. During the breeding season, the ewes immunized against pig inhibin alpha-subunit showed higher antibody titres compared with the group immunized against inhibin-like peptide (P < 0.01) and a significant increase in ovulation rate (12.1) compared with both the control (5.0; P < 0.05) and the inhibin-like peptide-immunized group (3.1; P < 0.01). Immunization against pig inhibin alpha-subunit increased transferable embryo yield 4.5-fold (6.7 versus 1.5; P < 0.01) and improved embryo quality (94.6 versus 40.6%; P < 0.01). During the non-breeding season, immunization against pig inhibin alpha-subunit enhanced ovulation rate from 2.6 in the controls to 9.4 (P < 0.01) but did not affect transferable embryo production (3.9 versus 2.1; P > 0.05) and significantly lowered their quality (54.1 versus 100%; P < 0.01). In conclusion, active immunization against pig inhibin alpha-subunit can improve superovulatory response during the breeding season, while it appears to be unable to increase embryo yield during the seasonal anoestrus.

Anestrus↗

Histogenesis in the metacestode of Echinococcus vogeli and mechanism of pathogenesis in polycystic hydatid disease.

Histogenesis of the metacestode of Echinococcus vogeli was traced mainly in rodents inoculated intraperitoneally with finely minced infective vesicles. The fragments aggregated in the peritoneal cavity and coalesced, forming structures (plaques) from which primary vesicles arose. From primordia in their germinal tissue, exogenous vesicles developed, enlarged, and migrated outward to the surface of the laminated membrane, where they remained attached and proliferated. Each unit of vesicles so formed retained discrete identity and, within 6-8 mo, acquired an adventitia; thereafter, exogenous multiplication ceased and endogenous proliferation supervened. Large numbers of daughter cysts arose in the germinal tissue lining chambers within the units; endogenous proliferation also finally ceased, and the daughter cysts produced brood capsules containing protoscoleces. Primordia of exogenous vesicles were not observed in the walls of daughter cysts. Production of protoscoleces involved 3 processes: they developed in typical brood capsules, singly in minute brood capsules, or directly from germinal tissue. Exogenous proliferation is not characteristic in the natural intermediate host of E. vogeli, the paca. Evidently in primates, the initial proliferation in the liver is followed by extension of the metacestode into the peritoneal cavity and eventual invasion of abdominal and thoracic organs. Exogenous proliferation by a process unique to E. vogeli accounts for the clinical course of polycystic hydatid disease.

Animals↗

Optimal pH for simple cold storage or machine perfusion of dog kidneys with UW solution.

Metabolic suppression by temperature is a key to successful organ preservation. Additional methods for inducing metabolic suppression may further improve organ preservation. Extracellular acidosis has been shown to suppress warm anoxic injury to various isolated cells. Acidosis may suppress enzymes with a pH optimum at the pH of the cytosol (pH 7.3). In this study, the combination of hypothermia and acidosis was used to determine if it would improve renal preservation. Dog kidneys were cold-stored (CS) for 48 h in University of Wisconsin (UW) solution with the pH adjusted to 6.4, 6.8, 7.4, or 7.8. Kidneys were also machine-perfused (MP) for 3 days with the gluconate perfusion solution (Belzer's machine perfusion solution, MPS) at pHs similar to those tested for CS. Renal function (serum creatinine, SCr) and survival were recorded in immediate contralateral nephrectomized recipients. On the basis of maximum SCr values, kidneys preserved by CS or MP were best preserved at pHs of 7.4 or 7.8. At a pH of 6.8, SCr values were elevated and returned to normal at a slower rate than in those preserved at higher pHs. This study shows that acidosis is not cytoprotective to cold-stored dog kidneys and causes preservation/reperfusion injury.

Adenosine↗

Tumor necrosis factor-alpha and interleukin-8 release from U937 human mononuclear cells exposed to zinc oxide in vitro. Mechanistic implications for metal fume fever.

Respiratory exposure to zinc oxide results in metal fume fever, a flu-like illness characterized by dose-dependent increases in pulmonary tumor necrosis factor-alpha (TNF) and interleukin-8 (IL-8). To examine whether mononuclear cells are a source of these proinflammatory cytokines, we exposed U937 cells to zinc oxide in vitro. Cell culture supernatant TNF and IL-8 was measured after 3, 8, and 24 hours of exposure to zinc oxide in varying concentrations. Zinc oxide exposure in vitro led to TNF release in a dose-dependent manner at 3, 8, and 24 hours (analysis of variance [ANOVA] P = 0.0001). IL-8 demonstrated a statistically significant zinc exposure response at 8 hours (ANOVA P = 0.005) and 24 hours (ANOVA P = 0.02). IL-8 at 8 hours correlated with 3-hour TNF levels (r = 0.52, P = 0.04). These data demonstrate that in vitro zinc oxide exposure stimulates U937 mononuclear cells to release TNF and IL-8 consistent with in vivo observations in metal fume fever.

Cells, Cultured↗

Neotropical echinococcosis in Suriname: Echinococcus oligarthrus in the orbit and Echinococcus vogeli in the abdomen.

This paper reports two cases of neotropical echinococcosis caused by Echinococcus oligarthrus and E. vogeli, neither of which has been reported from Suriname. Case 1, a six-year-old boy, presented a 15 x 25 mm retro-ocular cystic tumor (observed by ultrasound, computed tomography scan, and magnetic resonance imaging) causing exophthalmia, chemosis, palpebral ptosis, and blindness of the left eye. Of two tentative diagnoses, Echinococcus cyst or dermoid tumor, the former was shown to be correct at surgery when a clear liquid and detached protoscoleces were aspirated. Rostellar hooks of the protoscolex were characteristic of E. oligarthrus. Case 2, a 41-year-old man, had polycystic masses excised from the liver and abdomen. A presurgery diagnosis of E. vogeli infection was made due to calcifications seen in the lesions, positive serology, residence of the patient in the tropical forest, and later by the size and shape of rostellar hooks. The presence of these two parasites in one of the former Guianas is not surprising; both species are endemic in tropical forest in Central and South America wherever people have not exterminated wild canids, especially the bush dog, (Speothos venaticus), and felids (wild cats of several species), along with pacas, agoutis, and other rodents that serve as intermediate host of these two cestodes. Eighty-six cases of polycystic echinococcosis are known in people from 11 countries from Nicaragua to Argentina: 32 due to E. vogeli, three to E. oligarthrus, and 51 for which determination of the species was not possible because the hooks of the protoscolex were not found or described. Research to elucidate aspects of transmission of E. vogeli and E. oligarthrus is of practical importance for defining measures for preventing the severe and frequently fatal illnesses caused by these two cestodes.

Abdomen↗

A cryptic protease activity from Trypanosoma cruzi revealed by preincubation with kininogen at low temperatures.

Cysteine proteases have been identified in parasitic protozoa including the causative agent of Chagas' disease Trypanosoma cruzi. T. cruzi lysates subjected to substrate-containing SDS-polyacrylamide gel electrophoresis exhibit major bands of proteolytic activity in the 45-55 kDa molecular mass range (cruzipain activity). Paradoxically, addition of kininogen (a cystatin-like protease inhibitor) to the lysates before electrophoresis results in the appearance of additional bands of proteolytic activity in the 160-190 kDa molecular mass range. This inhibitor-activated protease activity depends upon the reaction conditions and exhibits novel properties. For example, a 24-48 hour preincubation at low temperature (-20 degrees C optimum) greatly enhances the proteolytic activity. The results suggest that a metastable complex forms between kininogen and a cryptic 30 kDa cysteine protease from T. cruzi and that this complex participates in the activation of proteolytic activity.

Animals↗

Polycystic echinococcosis in tropical America: Echinococcus vogeli and E. oligarthrus.

The paper reports available data on 72 known human cases of polycystic echinococcosis (PE) caused by Echinococcus vogeli (Ev) or E. oligarthrus (Eo). The patients' ages ranged from 6 to 78 years (median 44); one third were younger than 22 years and had severe lesions, demonstrating the aggressiveness of PE. There were no differences in occurrence between sexes. In 80% of the cases the lesions were in the liver alone or in combination with other organs; the rest were located in the lung or other single sites. The diagnosis of PE was based on the demonstration of polycystic larval cestode lesions by radiological imaging (X-ray, US, CT scan) in patients born in tropical sylvatic areas of America where wild carnivores (canids, felids) and rodents (pacas and other species) were present. Serologic tests often, but not always, supported the diagnosis. Species identification of Ev or Eo were based on morphological characteristics of rostellar hooks from protoscoleces. The most common clinical presentation was abdominal; hard, round masses in or connected with the liver, hepatomegaly, increased abdominal size, pain, marked weight-loss and fever. Signs of portal hypertension were also present in 25% of cases, all of whom died of the disease or surgical complications following biliary drainage or partial hepatectomy. Ten percent were in asymptomatic persons. Albendazole treatment resulted in clinical improvement and disappearance or reduction of the size of lesions in some patients observed up to 24 months. The author believes that albendazole treatment should be tried before any other treatment is implemented. Human PE was reported from 11 countries, from Nicaragua to Argentina, 31 case were due to E. vogeli, three to E. oligarthrus (two orbital from Venezuela and Surinam and one cardiac from Brazil) and 38 were due to Echinococcus sp. (no rostellar hooks were available). PE reported from Nicaragua, Costa Rica, Chile, Argentina and Uruguay, countries outside the geographical range of the bush dog (only natural host of Ev) may have been due to Eo rather than to Ev. Several felids are known to serve as final host of Eo, and they are present in those areas. Epidemiological field studies of autochthonous human populations in tropical areas may contribute to early detection and make possible greater success in treatment of polycystic echinococcosis.

Adult↗

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↗