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Biomedical subjects

E Isolauri

Publications and source records attributed to E Isolauri.

At least 127 records · Page 7Linked to original sources

Enhancement of the circulating antibody secreting cell response in human diarrhea by a human Lactobacillus strain.

Human Lactobacillus sp strain GG (Lactobacillus GG) administered during acute rotavirus diarrhea has been shown to promote clinical recovery. To elucidate the immune mechanisms behind such a favorable outcome, the ELISPOT (solid phase enzyme-linked immunospot) assay of Ig- and specific antibody-secreting cells among circulating lymphocytes was used, giving indirect evidence of the immunologic events in the gut. After rehydration, 39 children with acute rotavirus diarrhea, mean age 16 (SD 6) mo, randomly received either a Lactobacillus GG fermented milk product (study group) or a pasteurized yogurt (placebo group). The duration of diarrhea was significantly shorter in the study group than in the placebo group [mean 1.1 (SD 0.6) versus 2.5 (SD 1.4)d, p = 0.001]. Lactobacillus GG therapy was associated with a significantly enhanced nonspecific humoral response during the acute phase of the infection, reflected in the IgG, IgA, and IgM Ig-secreting cell numbers. At convalescence, 90% of the study group versus 46% of the placebo group had developed an IgA specific antibody-secreting cell response to rotavirus (p = 0.006). The results indicate that Lactobacillus GG promotes recovery from rotavirus diarrhea via augmentation of the local immune defense. Furthermore, specific IgA response to rotavirus is endorsed, which is possibly relevant in protection against reinfections.

Animals↗

Early dietary antigens delay the development of gut mucosal barrier in preweaning rats.

To determine the effects of early antigen exposure on the maturation of the gastrointestinal mucosal barrier, rat pups were divided into three groups at the age of 14 d. In addition to normal maternal milk, group CM (n = 24) received daily a gavage feed of cow's milk and group PH (n = 20) a whey protein hydrolysate during the experimental feeding period (14-20 d). Controls (n = 15) remained on maternal milk only. At 21 d, when "gut closure" normally occurs, intestinal absorption of horseradish peroxidase (HRP), was examined in vitro in Ussing chambers. The absorption of intact HRP [geometric mean (95% confidence interval)] was significantly higher in group CM [35.3 (16.7, 74.7) ng.h-1.cm-2] than in group PH [5.2 (1.4, 19.5) ng.h-1.cm-2] and in controls [3.4 (0.8, 15.1) ng.h-1.cm-2; F = 5.54, p = 0.006]. The absorption of degraded HRP was comparable in all groups. There were no modifications in electrical parameters in association with increased mucosal permeability to HRP. Furthermore, in group CM electron-microscopic studies disclosed accumulation of HRP in the cytoplasm of the epithelial cells and in the intercellular spaces where cell junctions remained unaltered. These results indicate that early administration of antigens delays the process of gut closure. They further suggest that continuously enhanced endocytosis of macro-molecules is induced by an insult to the mucosa as part of the host response to these antigens, irrespective of the protection afforded by maternal milk.

Animals↗

Increased beta-lactoglobulin absorption during rotavirus enteritis in infants: relationship to sugar permeability.

We studied absorption of the potentially allergenic protein beta-lactoglobulin during acute rotavirus diarrhea in infants and assessed the relationship of this macromolecular absorption with intestinal sugar permeability. After oral rehydration, 38 patients with acute gastroenteritis were given orally a 100-ml solution containing 4 g (11.7 mmol/L) of lactulose and 0.8 g (4.4 mmol/L) of mannitol, and their recovery rate as shown in urine passed during the subsequent 5 h was measured. A blood sample was taken 2 h after a milk feed for ELISA measurement of beta-lactoglobulin in circulating immune complexes. Twelve nondiarrhea patients were studied after an overnight fast as controls. Immune complexes containing beta-lactoglobulin were found in the serum of all, but the levels [median (range)] were significantly higher in patients with rotavirus diarrhea [686 (36-4352)] than in nondiarrhea patients [165 (0-2594)]; p = 0.007. The mean (95% confidence interval) lactulose/mannitol urinary recovery ratios were increased in patients with acute diarrhea [0.19 (0.10, 0.30)] compared to nondiarrhea patients [0.01 (0.005, 0.02)]; p = 0.0001. Thus, a significant correlation between beta-lactoglobulin absorption and sugar permeability was found; Spearman's rank correlation coefficient = 0.42, p = 0.004. This correlation was not, however, direct but was due to an inverse relationship between urinary recovery of mannitol and serum beta-lactoglobulin immune complexes. These results indicate that rotavirus gastroenteritis is associated with enhanced beta-lactoglobulin absorption and elevated lactulose/mannitol permeability test results, but these represent different phenomena.

Antigen-Antibody Complex↗

A human Lactobacillus strain (Lactobacillus casei sp strain GG) promotes recovery from acute diarrhea in children.

To determine the effect of a human Lactobacillus strain (Lactobacillus casei sp strain GG, Gefilac) on recovery from acute diarrhea (82% rotavirus), 71 well-nourished children between 4 and 45 months of age were studied. After oral rehydration, the patients randomly received either Lactobacillus GG-fermented milk product, 125 g (10(10-11) colony-forming units) twice daily (group 1); Lactobacillus GG freeze-dried powder, one dose (10(10-11) colony-forming units) twice daily (group 2); or a placebo, a pasteurized yogurt (group 3) 125 g twice daily; each diet was given for 5 days, in addition to normal full diet otherwise free of fermented dairy products. The mean (SD) duration of diarrhea after commencing the therapy was significantly shorter in group 1 (1.4 [0.8] days) and in group 2 (1.4 [0.8] days) than in group 3 (2.4 [1.1] days); F = 8.70, P less than 0.001. After rehydration, each dietary group maintained a positive weight trend. The urinary lactulose-mannitol recovery ratios (means [95% confidence intervals]) on admission were 0.09 (0.03, 0.24) in group 1, 0.12 (0.07, 0.22) in group 2, and 0.08 (0.04, 0.18) in group 3; no significant alterations in intestinal permeability were observed at retesting after 2 days of realimentation. The result indicates that early nutritional repletion after rehydration causes no mucosal disruption and is beneficial for recovery from diarrhea. It is further suggested that Lactobacillus GG in the form of fermented milk or freeze-dried powder is effective in shortening the course of acute diarrhea.

Acute Disease↗

Antigen absorption in rabbit bacterial diarrhea (RDEC-1). In vitro modifications in ileum and Peyer's patches.

Intestinal absorption of antigenic (intact) and degraded beta-lactoglobulin and horseradish peroxidase was studied in rabbits experimentally infected at weaning with the rabbit-specific Escherichia coli strain RDEC-1 (015:NM). Transepithelial fluxes of both proteins were measured at four stages after infection: early, peak, late, and recovery, on segments of ileum and Peyer's patches mounted in Ussing chambers. During this period of observation, absorption of antigenic beta-lactoglobulin and intact horseradish peroxidase decreased significantly in the ileum and Peyer's patches of age-matched controls. No significant age-related decrease was observed in the controls for the transport of these proteins in degraded form. RDEC-1 infection caused, first, a rise in degraded protein fluxes across Peyer's patches only, during the early phase of the disease. Second, during the peak phase of infection, absorption of antigenic beta-lactoglobulin by the ileum rose to 74.0 ng/hr/cm2 (90% confidence interval: 63.1, 86.8) vs 15.8 (5.8, 42.8) in the controls (P = 0.07), and absorption of intact horseradish peroxidase rose to 21.8 (16.5, 26.7) ng/hr/cm2 vs 4.4 (0.7, 26.6) in control ileum, (P = 0.09). These rises, which were similar in Peyer's patches, delayed the physiologic decrease in protein absorption that occurs with age. These results indicate that increased antigen absorption is observed during bacterial diarrhea and that it might interfere with the immune responses of the host.

Animals↗

Development of the neonatal rat small intestinal barrier to nonspecific macromolecular absorption: effect of early weaning to artificial diets.

We studied the effect of early weaning from maternal breast milk to artificial diets on rat jejunal absorption of an exogenous 40-kD glycoprotein, horseradish peroxidase (HRP). Rat pups, fed maternal milk (MM) from birth, received one of three diets for the last 4 d before weaning (d 17-21): MM, protein hydrolysate formula (PH), or soy formula (S). Some rats were pretreated on d 14 with intraperitoneal hydrocortisone (5 mg/rat). In MM-fed rat pups, jejunal HRP absorption was markedly higher on d 17 than on d 21. [Geometric means (95% confidence interval) were: d 17, 626.4 (461.3, 850.6) versus d 21, 90.6 (48.2, 170.5) IU HRP/mL x cm x min, p less than 0.01.] By contrast, 21-d-old PH- and S-fed pups maintained elevated absorption of the tracer [PH, 292.3 (177.5, 480.6), p less than 0.05 versus MM pups, S, 340.8 (164.4, 704.8), p less than 0.01 versus MM pups]. Wt-matched control studies indicate that the difference in HRP absorption was not due to the smaller body wt of formula-fed pups. The increased absorption in formula-fed animals was suppressed by hydrocortisone. In S-fed pups, the increased macromolecular absorption appeared, in part, to be the result of diffusion across altered villus absorptive cells. In PH-fed pups, there was no evidence of damage and HRP absorption appeared to occur by vesicle-mediated transport. Delay in the normal maturation of small intestinal "closure" appears to be associated with early weaning to artificial diets. This may lead to increased nonspecific macromolecular permeability that could result in immune-mediated sensitization and food intolerance.

Age Factors↗

Local immune response measured in blood lymphocytes reflects the clinical reactivity of children with cow's milk allergy.

Study was made of immune responses in cow's milk allergy by a new immunoassay that measures total Ig-secreting cells and specific antibody-secreting cells during their maturation cycle in peripheral blood. These primed gut-associated lymphoid tissue-derived lymphocytes are assumed to reflect the intestinal immune responses. During diagnostic milk provocation, 15 patients had acute urticarial skin eruptions, eight patients had slow onset of eczema, and 15 showed symptoms from the gastrointestinal tract. A significant increase in IgM-secreting cells (means with 95% confidence intervals) from 382.2 (265, 552) to 621.4 (381, 1013)/10(6) cells, p less than 0.01, but not IgA- and IgG-secreting cells was associated with acute urticaria. In patients with eczematous skin eruptions and gastrointestinal symptoms, the response involved all these Ig isotypes. The magnitude of the postchallenge Ig-secreting cell responses in patients with gastrointestinal symptoms in the IgM class [from 657.9 (428, 1012) to 3544.0 (1696, 7406)/10(6) cells, p less than 0.001] and the IgA class [from 974.6 (590, 1610) to 2482.4 (1528, 4028)/10(6) cells, p = 0.001] significantly exceeded that of the patients with cutaneous symptoms. Notwithstanding the distinct increase in the total number of Ig-secreting cells, the specific antibody-secreting cell response specifically directed against beta-lactoglobulin and alpha-casein was small and inconsistent. These findings indicate that immune exclusion of milk antigens is defective in cow's milk allergy. The quality and extent of the response varied in the three reaction types, suggesting that different immunopathogenic mechanisms are operative in cow's milk allergy.

Animals↗

Intestinal permeability changes in acute gastroenteritis: effects of clinical factors and nutritional management.

The effects of early home management of acute diarrhea followed by rapid in-hospital realimentation on intestinal permeability were studied in 41 children aged 3-25 months with acute gastroenteritis (73% rotavirus). After oral rehydration, a 100 ml oral load containing 4 g of lactulose and 0.8 g of mannitol was administered, and an aliquot of urine excreted in the subsequent 5 h was analyzed with gas-liquid chromatography. The mean lactulose/mannitol recovery ratio was significantly higher than in 28 nondiarrheal controls, which was due to decreased mannitol excretion. The gastroenteritis patients who had received uninterrupted feeding in addition to adequate fluid replacement before hospitalization had a normal urinary lactulose/mannitol ratio, with a mean of 0.04, and a 95% confidence interval (CI) of [0.03, 0.07], whereas in fasted children with inadequate or adequate fluid replacement, the respective mean ratios were 0.24, 95% CI of [0.14, 0.43], and 0.14, 95% CI of [0.09, 0.20] (F = 12.63, p less than 0.001). The fasting-associated rise was caused by increased lactulose excretion. At retesting of gastroenteritis patients after 2 days of in-hospital realimentation, the lactulose/mannitol ratios did not differ significantly from the level on admission. The study indicated that fasting maintains the increased intestinal permeability associated with acute gastroenteritis whereas early feeding at home may promote reduction of permeability and hasten recovery.

Acute Disease↗

Neonatal septicaemia in Finland 1981-85. Predominance of group B streptococcal infections with very early onset.

A survey of blood culture-confirmed neonatal septicaemia was carried out in seven delivery hospitals in 1981-85, for a second successive five-year period. The total number of cases was 377, to compare with 410 in the previous five-year period. Group B streptococcus (GBS) was throughout the major pathogen (29%), followed by Staphylococcus aureus (15%) and Escherichia coli (14%), while Staphylococcus epidermidis (10%) has emerged as a significant new causative agent. Septicaemia with very early onset was predominant: 49% of the cases had onset within the first 24 hours; in the majority the symptoms were present from birth. GBS was responsible for 49% of the cases detected in the first 24 hours of life. The overall mortality was 20% as compared to 23% in the previous five-year period, whereas in the very early onset septicaemia mortality was now 18%, down from the preceding 30%. Despite the modest progress, GBS septicaemia with very early onset remains a significant problem, and effective preventive measures are needed.

Finland↗

Acute gastroenteritis. Changing pattern of clinical features and management.

During seven epidemics of rotavirus from 1978 to 1987, 575 children younger than 3 years were admitted to hospital with acute gastroenteritis. The management before and during hospitalization, the status on admission and the outcome are reviewed. The mean age of the patients rose significantly during the study period, with the proportion younger than 12 months decreasing from 50 to 26%. Mild to moderate iso-osmolal dehydration was found in most cases, both hypernatraemia and hyponatraemia were rare. The home management had usually consisted of fasting except for "clear fluids". Oral rehydration and rapid feeding in hospital according to modern principles accelerated weight gain, shortened the duration of diarrhoea and the hospital stay and reduced the requirement for intravenous fluid therapy. This experience, together with the current rarity of acute gastroenteritis in young infants and of delay in recovery, suggests that oral rehydration and realimentation should be more extensively used in general practice.

Acute Disease↗

Antigen absorption in bacterial diarrhea: in vivo intestinal transport of beta-lactoglobulin in rabbits infected with the entero-adherent Escherichia coli strain RDEC-1.

We studied the absorption of both antigenic and degraded beta-lactoglobulin (beta-LG) from the ileum to the portal blood, in rabbits infected at weaning with the entero-adherent Escherichia coli strain RDEC-1. The infection was characterized by high bacterial excretion from days 7 to 18 postinfection (pi), acute diarrhea for 10 days, and considerable growth retardation. Intestinal absorption of beta-LG was measured at four stages of the infection: early (day 3 pi), peak (day 10 pi), late (day 18 pi), and recovery (day 30 pi). During the 30-day period of infection, age-matched control rabbits exhibited a significant decrease in antigenic and degraded beta-LG absorption. In both control and infected animals, more than 90% of the beta-LG was absorbed by a degrading pathway and the remainder in antigenic form by a minor pathway. RDEC-1 infection significantly raised antigenic beta-LG absorption from days 10 to 30 pi, which delayed the decrease that normally occurs with age. Degraded beta-LG absorption was not modified by the infection, except for a slight increase observed at the recovery stage (day 30 pi). These results suggest that RDEC-1 diarrhea increases absorption of food antigens. The subsequent local or systemic immune responses are not known, but pathologic consequences are possible in susceptible individuals.

Animals↗

Clinical trials of rotavirus vaccines.

The clinical efficacy of candidate rotavirus vaccines has been tested in Tampere, Finland, over four winter and spring rotavirus epidemic seasons in 1983-1986. Testing against natural challenge has demonstrated that heterologous oral rotavirus vaccines induce cross-protection to human rotavirus diarrhoea. The trials have also given insight into mechanisms of protection in human rotavirus diarrhoea. After the oral vaccination of infants aged six to 12 months the highly attenuated bovine rotavirus strain RIT 4237, titre 10(8) per dose, probably 'takes' in most vaccinees, producing a symptomless intestinal infection with a low virus excretion rate and an antibody response in over 80% of the initially seronegative subjects. Upon natural challenge such vaccination gives no protection against human rotavirus infection but gives 50-60% protection against any clinically detectable rotavirus-associated illness and 80-90% protection against severe rotavirus diarrhoea, regardless of the infecting human rotavirus serotype. The less attenuated rhesus monkey rotavirus RRV-1, titre 10(5)-10(6) per dose, is more infectious in humans, and virus multiplication in the intestine results in excretion of vaccine virus in the stools and some clinical symptoms, mainly fever, 3-4 days after vaccination. The degree of protection against human rotavirus diarrhoea appears similar to that induced by bovine rotavirus vaccine.

Antibodies, Viral↗

Immunogenicity and safety of a low passage level bovine rotavirus candidate vaccine RIT 4256 in human adults and young infants.

A candidate rotavirus vaccine RIT 4256, derived from Nebraska calf diarrhea virus by 21 tissue culture passages, was tested in humans and compared with the RIT 4237 vaccine derived from the same stem virus by 147 tissue culture passages. The low passage strain RIT 4256 was first tested in adult volunteers for immunogenicity and safety: a serological response was seen in 9/18 (50%) vaccinees; three subjects had a mild fever reaction attributable to the vaccine. In 6 month old children the RIT 4256 vaccine elicited a serological response in 12 of the 21 (57%) seronegative recipients; two children had a possible fever reaction from the vaccination. In newborn infants a serological response following vaccination was detected in 19/41 (46%) of the recipients of the RIT 4256 and in 19/40 (48%) of the RIT 4237 vaccine; none of the newborn infants had any reaction from either vaccine. It is concluded that the low passage strain RIT 4256 is not more immunogenic than the high passage vaccine RIT 4237 in humans. The vaccines do not differ in clinical reactogenicity for man.

Adult↗

A comparative trial of rapid oral and intravenous rehydration in acute diarrhoea.

37 children under the age of 5 years hospitalized for acute diarrhoea and dehydration were randomized to receive oral or intravenous rehydration during 6 to 12 hours. Rehydration was satisfactory in both groups, with correction of dehydration, metabolic acidosis and sodium deficit at equal rates. The reintroduction of normal feedings was successful in most of the orally rehydrated children after 12 hours, but often unsuccessful in the i.v. therapy group. Consequently the orally rehydrated children showed a 2.9% weight gain by the time of discharge whereas the intravenously treated children did not gain weight in the hospital. The duration of diarrhoea was also shorter in the orally rehydrated children. Thus oral rehydration therapy was equal or superior to even rapid intravenous rehydration therapy in the management of acute diarrhoea in children.

Acute Disease↗