Biomedical subjects

H G Folkesson

Publications and source records attributed to H G Folkesson.

8 recordsLinked to original sources

PubMed1992

Increased passage of bovine serum albumin over the respiratory tract after intratracheal instillation during septic shock in rats.

Sepsis may initiate acute respiratory distress syndrome which may be accompanied by an increased pulmonary epithelial-endothelial permeability. In this study, sepsis was induced by an intraperitoneal implantation of gelatine capsules containing Escherichia coli/Bacteroides fragilis/adjuvant substance. The importance of bacteria in sepsis-related lung injury was studied in rats given an intraperitoneal injection of E. coli or in rats given the adjuvant substance alone in capsules intraperitoneally. Rats with empty capsules were used as controls. The rats were intratracheally instilled with bovine serum albumin (BSA) directly after the capsule implantation or the injection of E. coli, and the passage over the lower respiratory tract was assessed as blood plasma levels of immunoreactive BSA. The plasma BSA levels in the control rats increased continuously up to 24 h after intratracheal instillation. This increase was significantly augmented already 1 h after the septic challenge, i.e. before any clinical symptoms were observed, in both the septic rats and the rats with the E. coli injected intraperitoneally. Furthermore, the time required to obtain maximal plasma BSA levels was shorter in septic, adjuvant-exposed and in E. coli-injected rats than in the controls. The plasma levels and the total BSA passage over the lower respiratory tract was significantly higher (p less than 0.001) in the septic and in the E. coli-injected rats than in the adjuvant-exposed and the control rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Lung to blood passage of human growth hormone after intratracheal instillation: stimulation of growth in hypophysectomized rats.

The passage from the lower respiratory tract into the blood of human GH (hGH; M(r) = 22,000) and bovine serum albumin (BSA; M(r) = 67,000) was assessed after intratracheal instillation in adult rats. The plasma level of immunoreactive hGH reached its maximum at 0.5-1 h after instillation and had almost disappeared within 24 h. Higher plasma levels were obtained in male rats than in female rats resulting in a higher total lung passage of hGH in male rats than in female rats (means +/- S.D.; 6.0 +/- 1.7% vs 3.3 +/-1.2%, P<0.01). The plasma level of BSA showed a different pattern, with a maximum at 16-24 h after instillation and a total lung passage of 4.3 +/- 1.7% of the given dose for both sexes. The plasma levels of hGH increased nonlinearly with increasing dose instilled in the dose range 36-720 micrograms/kg body weight. When hGH was instilled daily at a dose of 720 micrograms/kg body weight to hypophysectomized rats for 1 week, they responded with a significant increase in body weight when compared with hypophysectomized control rats (16.8 +/- 4.2 g vs -1.8 +/- 2.4 g, P<0.001). The results demonstrate that, despite their different molecular weights, hGH and BSA pass through the lower respiratory tract into the circulation with similar efficiencies in the rat. However, the lung passage of hGH, unlike that of BSA, showed sexual dependency, an earlier plasma concentration maximum and a tendency of the passage to saturation with increasing dose instilled.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Lung to blood passage of different-sized molecules during lung inflammation in the rat.

The passage of different-sized marker molecules over the lower respiratory tract into the blood circulation during pulmonary inflammation induced by dextran, endotoxin [i.e., lipopolysaccharide from Escherichia coli (LPS)], or ferritin was assessed in the rat. Bovine immunoglobulin G (BIgG, mol wt = 150,000 Da), bovine serum albumin (BSA, mol wt = 67,000 Da), and the nonapeptide 1-deaminocysteine-8-D-arginine vasopressin (dDAVP, mol wt = 1,067 Da) were used as permeability markers after intratracheal instillation. The pathophysiological indexes of a proceeding lung inflammation were increased total cell number, changed leukocyte proportions and increased total protein content obtained in bronchoalveolar lavage, and lung edema formation shown as an increased lung wet-dry weight difference. Intratracheal instillation of dextran induced a moderate neutrophil invasion into the lungs but had no effect on the passage of the different markers over the lungs (BIgG 1.8 +/- 0.6%, BSA 3.5 +/- 1.2%, dDAVP 26.1 +/- 20.7%) compared with control rats instilled with the markers alone (1.8 +/- 0.4%, 4.1 +/- 1.3%, 20.0 +/- 3.8%, respectively). Endotoxin administration resulted in markedly higher lavage cell counts and lung edema concomitantly with an increased lung passage of the markers (3.2 +/- 0.9%, 22.0 +/- 6.1%, 33.3 +/- 12.0%, respectively; P less than 0.01-P less than 0.001). The highest marker passage was obtained when the inflammation was most severe, i.e., after ferritin administration (17.6 +/- 2.3%, 60.0 +/- 6.7%, 41.6 +/- 6.9%, respectively; P less than 0.001), which resulted in markedly elevated lavage cell numbers and protein content as well as edema formation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1990

Permeability of the respiratory tract to different-sized macromolecules after intratracheal instillation in young and adult rats.

The markers, bovine IgG (BIgG, mol. wt = 150,000 Da) and bovine serum albumin (BSA, mol. wt = 67,000 Da) together with 1-deamino-cysteine-8-D-arginine vasopressin (dDAVP, mol. wt = 1067 Da), were intratracheally instilled into young and adult rats and their passages via the respiratory tract were assessed as immunoreactive marker levels in blood serum. In the adult rats (100-120 days old) the BSA serum levels peaked 16-24 h after instillation and with a calculated transferred amount (bioavailability) of 4.3 +/- 1.7 to 5.6 +/- 1.4% of the dose given (five resp. 50 mg kg-1 body wt). BIgG passed via the respiratory tract with a maximum at 16 h, and with a transferred amount of 1.5 +/- 0.3%, while dDAVP serum levels peaked at 1 h and with a transferred amount of 20 +/- 4%. For the 30-day-old rats, similar passage time curves were obtained as for the adult, but the transferred amount was lower for BIgG (0.7 +/- 0.3%), similar for BSA (4.1 +/- 1.1%) and higher for dDAVP (45 +/- 16%). The serum levels of BSA increased linearly with increasing dose instilled (2.5-200 mg kg-1 body wt), indicating a passive transepithelial transport route. The results show that macromolecules pass via the respiratory tract into the circulation of the rat in mainly intact forms and in high amounts, compared with passage via the GI tract. There appears to exist an inverse relationship between the molecular weights of instilled molecules and the transferred amount, a relationship affected by the development of the lung.

Aging↗

PubMed1989

Degradation of [mercaptopropionic acid1, D-arginine8]-vasopressin (dDAVP) in pancreatic juice and intestinal mucosa homogenate.

The degradation of the vasopressin analogue dDAVP was studied by reversed phase high-performance liquid chromatography (HPLC) after incubations in pancreatic juice and intestinal mucosa homogenates. dDAVP remained stable in pancreatic juice for a period of 60 min. while the parent hormone arginine vasopressin (AVP) was completely degraded within 5 min. In intestinal mucosa homogenates dDAVP was degraded with half-lives of 9 min. (fast phase) and 161 min. (slow phase), about four times slower than AVP. By amino-acid analysis it was confirmed that the metabolite [Mpa1, Des-D-Arg8-Gly9 NH2]-vasopressin was gradually produced. No other breakdown products were observed. These findings may be of value for the further development of more stable peptide analogues which may be effective upon oral administration.

Animals↗

PubMed1989

Decrease in intestinal permeability to polyethylene glycol 1000 during development in the pig.

Changes in intestinal permeability during postnatal development in the pig were investigated by using different-sized polyethylene glycols in the Mr 766-1338 range (polyethylene glycol 1000) as permeability probes. Pigs of varying age, newborn (Oh), 36-45 h old and 22-28 days old, were gavage fed polyethylene glycol 1000 together with the macromolecular markers bovine serum albumin, ovalbumin or FITC-labelled dextran 70,000. The 4-h blood serum concentrations of the different markers were determined and taken as an estimate of their intestinal transmission. In the newborn pigs, high serum levels of polyethylene glycols were obtained, concomitant with high serum levels of bovine serum albumin and FITC-dextran. After intestinal macromolecular closure in the 36-45 h-old pigs, lower serum polyethylene glycol levels were found, especially of those with a Mr greater than 1100 Da. In the 22-28 days-old pigs, polyethylene glycol levels were reduced to one-tenth or less of those in the 36-45 h-old pigs, with the levels decreasing markedly with increasing molecular size. These results show that there is a correlation between the intestinal permeability of polyethylene glycols, especially those larger than 1100, and macromolecules in the newborn pig around intestinal closure, suggesting that such polyethylene glycols traverse the gut by the macromolecular route. During later development, further intestinal maturation results in a markedly reduced permeability to polyethylene glycol 1000.

Aging↗

PubMed1988

Decreased passage of the nonapeptide dDAVP over the intestinal epithelium during development in the young rat.

The nonapeptide 1-deamino-cysteine-8-D-arginine vasopressin (dDAVP) was gavage-fed together with cow's milk whey protein to young, developing rats. The transepithelial passage of dDAVP in the gastrointestinal (GI) tract was assessed by a specific RIA as immunoreactive levels in blood serum extracts and as urinary excretion of dDAVP 0.5-8 h after feeding. In 14-day-old rats the passage of dDAVP was higher than in 30-day-old rats, since the 14-day-old rats had significantly higher serum levels (5-10 times) 0.5-2 h after feeding and a urinary excretion approaching 0.15% of the administered amount after 8 h. In the 30-day-old rats urinary excretion increased up to 0.05% after 2 h and then levelled off. It was also clear that 30-day-old rats had a slower transfer to and faster elimination from serum than 14-day-old rats. dDAVP appeared to be passed over the GI tract mucosa independently of intestinal proteolysis since feeding it to 30-day-old rats together with the proteinase inhibitors, soya-bean trypsin inhibitor and pepstatin did not influence the serum or urinary levels. Thus, dDAVP was taken up from the GI tract into the blood circulation and excreted in the urine of young rats. The decrease in the passage of dDAVP found around weaning appears to be related to developmental processes affecting the permeability of the intestinal epithelium rather than intestinal proteolysis.

Animals↗

PubMedDate not supplied

Passage of aerosolized BSA and the nona-peptide dDAVP via the respiratory tract in young and adult rats.

The passage of the protein marker, bovine serum albumin (BSA, MW = 67,000), and the nona-peptide, 1-deaminocysteine-8-D-arginine vasopressin (dDAVP, MW = 1067), from the respiratory tract into the blood when applied as an aerosol with a MMAD of 1.7 microns was studied in 14-, 30-, and 100-120-day-old (adult) healthy rats and in adult rats with lung injury. In blood serum of adult rats the levels of immunoreactive BSA reached its maximum 16-24 h after a 1-h aerosol exposure with a calculated total passage of 6.4 +/- 1.8% of the given dose. dDAVP serum levels measured by RIA peaked after 0.5-1 h, giving a total passage of 84.3 +/- 12.9%. With increasing exposure periods from 0.5 to 3 h, which thereby increased the lung burden, the serum levels of BSA and dDAVP increased linearly indicating passive transepithelial transport processes for both molecules. For the young rats, similar serum level-time curves were obtained like those of the adult, with similar total passages of BSA, 4.6 +/- 0.8% for the 14-day-old rats and 5.2 +/- 1.6% for the 30-day-old rats. For dDAVP the total passage was significantly lower in both the 14-day-old rats, 40.9 +/- 12.1%, and the 30-day-old rats, 16.7 +/- 6.1% (p less than .05), as compared to the adult rats. Acute lung inflammation induced in rats by intratracheal instillation of 5 mg ferritin/kg body wt prior to a 1-h marker aerosol exposure increased the passage of BSA (58.7 +/- 18.8%, p less than .05), while the dDAVP passage was less affected (99.2 +/- 25.2%, p greater than .05) as compared to the healthy adult rats. The results indicate that after aerosol exposure the total passage of dDAVP over the respiratory tract was higher than that of the macromolecule BSA, the passage appeared to increase with the maturity of the rats and by inflammatory changes in the lung tissue.

Aerosols↗