Biomedical subjects

P D Lundin

Publications and source records attributed to P D Lundin.

4 recordsLinked to original sources

PubMed1997

Bidirectional small intestinal permeability changes to different-sized molecules after HCl-induced injury in the rat.

A rat model was developed to assess bidirectional passage of macromolecules and low-molecular-weight markers across the intestinal barrier in intact and injured mucosa. Isolated in situ loops of distal small intestine were luminally perfused for 30 min with saline as control or HCI (pH 2.0) to induce an acute injury. The lumen-to-blood passage was followed during perfusion with bovine serum albumin, [14C]mannitol, and sodium fluorescein. Intravenously administered sodium fluorescein and endogenous serum albumin were used as blood-to-lumen markers. Acid exposure resulted in severe injury of the villi tips, with significantly increased lumen-to-blood passage of all markers compared with that of intact mucosa. Moreover, blood-to-lumen passage of rat serum albumin increased after the injury, while that of sodium fluorescein did not. The acid induced injury impaired the intestinal barrier function with an increased marker passage, where the macromolecules were more sensitive markers of the altered barrier function than low-molecular-weight markers.

Acute Disease↗

PubMed1997

Intestinal inflammation and barrier function in HLA-B27/beta 2-microglobulin transgenic rats.

BACKGROUND: Since intestinal inflammation is correlated with impaired barrier functions, transgenic HLA-B27/human beta 2-microglobulin rats that spontaneously develop intestinal inflammation were used to investigate whether onset of inflammation or impaired barrier function was the initial event. METHODS: During the age period of 9-14 weeks, transgenic and non-transgenic (control) rats were gavaged weekly with the marker molecules, 51Cr-ethylenediaminetetraacetic acid, 1-deamino-8-D-arginine vasopressin, and albumin, which were quantified in blood or urine. RESULTS: At 12 weeks of age the first signs of inflammation appeared with decreased body weight gain, decreased urine production, and onset of diarrhea. By 14-15 weeks of age all transgenic rats had developed intestinal inflammation, as confirmed by histology and increased myeloperoxidase content, whereas no inflammation was observed in controls. Intestinal passage of the markers did, however, not differ between transgenic and control rats over the studied period. CONCLUSIONS: The results suggest that intestinal inflammation precedes altered intestinal barrier function in this inflammation model.

Animals↗

PubMed1997

Enhancing effects of monohexanoin and two other medium-chain glyceride vehicles on intestinal absorption of desmopressin (dDAVP).

The intestinal absorption enhancement of the nonapeptide [Mpa1,D-Arg8]vasopressin (dDAVP) by medium-chain glyceride vehicles was studied using an in vivo rat model. Rats were gavaged with dDAVP formulated with three different lipid vehicles: (1) monohexanoin, (2) mixed monoglycerides, diglycerides and triglycerides of hexanoic acid and (3) monoglycerides, diglycerides and triglycerides of octanoic and decanoic acids, and with saline as control. The marker absorption into blood and urine was followed for 24 hr. All lipid vehicles enhanced the oral bioavailability of dDAVP, but monohexanoin gave the highest increase, approximately 10 times that of control. In contrast to dDAVP, the stable and more lipophilic nonapeptide analog [Mpa1,D-Tyr(ethyl)2,Val4,D-Arg8]oxytocin did not show increased urine recovery when formulated with monohexanoin. A 2-fold increase in urine recovery of the inert low-molecular-weight marker [51Cr]EDTA was observed when formulated with monohexanoin. With use of the fluorescent marker Evans blue formulated with monohexanoin, an elevated accumulation of Evans blue in the mucus layer was observed after incubation in in situ loops. No mucosal damage after lipid vehicle gavage was observed by light microscopic evaluation. Medium-chain glycerides functioned well as oral absorption enhancers of the model peptide dDAVP, and monohexanoin showed the highest enhancement capacity. The mechanisms of this enhancement appear to be related to a protection against luminal dDAVP degradation, mucoadhesive properties of the vehicle and, possibly, an altered epithelial absorption pathway.

Animals↗

PubMed1997

Pulmonary delivery of intratracheally instilled and aerosolized cyclosporine A to young and adult rats.

The delivery and pharmacokinetics of cyclosporine A (CyA) given locally to the airways or iv was evaluated in young and adult rats. After intratracheal (i.t.) instillation of saline suspended CyA to adult rats, the CyA plasma levels peaked at 30 min with a bioavailability of 78.1 +/- 6.9%. After the i.t. instillation of CyA with micelles forming surfactant, Cremophor EL, in adult and young rats, the plasma levels peaked at 5 min with a bioavailability of 77.5 +/- 7.2% and 66.3 +/- 4.5%, respectively. The bioavailability of aerosolized CyA was 80.1 +/- 4.1% in adults. Thus, CyA is absorbed by the lungs into the systemic circulation of the rat in high amounts, independent of age and type of delivery system. Long-term treatment with i.t. instillations did not affect body weight gain in young and adult rats, and no histopathological changes were found in the lungs. It is important to emphasize that CyA plasma clearance in young rats was lower and elimination half-life longer than in adults. The slow elimination of CyA in young rats indicated profound pharmacokinetic age differences for this species.

Aerosols↗