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- Arevalo Sureda, Ester
(författare)
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Development of the gastrointestinal tract in young mammals : Effects of enteral provocation with protease or phytohaemagglutinin in neonatal rats
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The rat, as an altritial species, is born with an immature gastrointestinal tract and intestinal barrier function, which is highly absorptive to milk-borne bioactive molecules that can pass undigested and reach the general circulation of the suckling newborn. This passage occurs by the neonatal-Fc-receptor (FcRn) binding and trancytosis of immunoglobulin G in the proximal small intestine (SI) and by the highly endocytic vacuolated enterocytes non-selectively in the distal SI. Postnatal gut maturation accelerates at weaning, around postnatal day 21, coincident with the dietary transition from milk to solid food. Maturation of the gut can also be precociously induced by provocation with a lectin, phytohaemagglutinin (PHA), mimicking the naturally occurring changes in gut structure and function. The changes occurring during natural or induced gut maturation include stimulation of pancreatic function and cessation of the SI absorptive capacity to macromolecules (gut closure). Intestinal epithelial maturation has been related to the gut immune system and is suggested to depend on T-lymphocytes activation. Recently, the transcription factor B-lymphocyte-induced maturation-protein-1 (Blimp-1) has been proposed to be a key regulator of intestinal maturation in mice. Hence, the present study investigated the events occurring during gut development and the cues initiating the process. The study especially focused on changes in the barrier function and macromolecular permeability, pancreatic function, and the relation to gut immune factors.A novel animal model of pancreatic and pancreatic-like protease-induced precocious gut maturation was established in neonatal rats, and was used in comparison to the existing PHA-induced model, as well as natural gut development. The gut maturational changes observed during natural or induced maturation, by both protease or PHA, included the transition of foetal- to adult- type SI epithelium, with reduced FcRn expression in the proximal part and disappearance of vacuolated enterocytes in the distal part, associated with a similar change in intestinal epithelial Blimp1 expression. The early effects after exposure to the provocative agents, PHA and protease, revealed that both agents hampered macromolecular permeability and only protease also caused an increase in epithelial leakiness of the distal SI. These results indicated that protease and PHA affected the intestinal barrier function differently. Furthermore, the provocative agents were also tested in neonatal athymic nude rats, T-cell immunodeficient, and they appeared to be susceptible to induced precocious gut maturation. These results suggested that gut maturation is independent of thymus-derived T-celsl, but the involvement of other immune cells types, possibly innate immune cells, should be further investigated.Thus, the findings of the present thesis will contribute to an increased understanding of initiating cues and the mechanisms of maturation of the intestinal barrier in young mammals. The knowledge obtained could be applied to improve strategies for the treatment of gut-related complications, often affecting premature infants.
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| 2. |
- Goncharova, Kateryna, et al.
(författare)
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Importance of neonatal immunoglobulin transfer for hippocampal development and behaviour in the newborn pig
- 2017
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 12:6
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Tidskriftsartikel (refereegranskat)abstract
- Neurological disorders are among the main clinical problems affecting preterm children and often result in the development of communication and learning disabilities later in life. Several factors are of importance for brain development, however the role of immunoglobulins (passive immunity transfer) has not yet been investigated. Piglets are born agammaglobulinemic, as a result of the lack of transfer of maternal immunoglobulins in utero, thus, they serve as an ideal model to mimic the condition of immunoglobulin deficiency in preterm infants. Thirty six, unsuckled newborn piglets were fed an infant formula or colostrum and supplemented orally or intravenously with either species-specific or foreign immunoglobulin and then compared to both newborn and sow-reared piglets. Two days after the piglets were born behavioural tests (novel recognition and olfactory discrimination of conspecifics scent) were performed, after which the piglets were sacrificed and blood, cerebrospinal fluid and hippocampi samples were collected for analyses. Both parameters of neuronal plasticity (neuronal maturation and synapse-associated proteins) and behavioural test parameters appeared to be improved by the appearance of species-specific porcine immunoglulin in the circulation and cerebrospinal fluid of the piglets. In conclusion, we postulate possible positive clinical effects following intravenous infusion of human immunoglobulin in terms of neuronal plasticity and cognitive function in preterm infants born with low blood immunoglobulin levels.
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| 3. |
- Sureda, Ester Arévalo, et al.
(författare)
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Induction of precocious intestinal maturation in T-cell deficient athymic neonatal rats
- 2017
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Ingår i: World Journal of Gastroenterology. - : Baishideng Publishing Group Inc.. - 1007-9327. ; 23:42, s. 7531-7540
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To investigate whether gut maturation could be induced precociously in an athymic T-cell deficient neonatal rat model. Methods: Fourteen day-old athymic (nude) rats (NIH-Foxn 1rnu) were gavaged with either phytohaemagglutinin - a lectin from red kidney beans (PHA); trypsin - a protease (Prot); or water - vehicle (control) as a single dose on one day or once a day for 3-day. The nude rats were either nurtured by their mothers or cross-fostered by conventional foster dams of the Sprague-Dawley strain from days 3-5 after birth. At 17 d of age, 72 h after administration of the first treatment, intestinal macromolecular permeability was tested in vivo, prior to euthanasia, after which blood and gut organs were sampled. Results: Provocation with both, PHA and protease, resulted in increased gut growth and maturation in nude rat pups independent of nursing. Foetal-type enterocytes were replaced by non-vacuolated adult-type enterocytes in the distal small intestine epithelium. Decreased intestinal macromolecular permeability (gut closure) was observed, with reduced permeability markers (BIgG and BSA, P < 0.001) in circulation. Increased pancreatic function, with an increased trypsin to protein ratio in pancreas homogenates, was observed independent of nursing in the nude pups. Immunostaining showed the presence of a few CD3+-cells in the intestinal mucosa of the nude pups. The number of CD3+-cells remained unaltered by provocation and no differences were observed between the nursing sets. Growth and vitality of the nude pups were dependent on nurturing, since cross-fostering by conventional dams increased their macromolecular absorptive capacity (BSA, P < 0.05), as well as their passive immunity (RIgG, P < 0.05). Conclusion: Precocious gut maturation can be induced by enteral provocation in athymic rat pups, similarly to in euthymic pups, thus showing an independence from thymusderived T-cells.
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