Changes in abdominal wounds following treatment with sirolimus and steroids in a rat model.

Wound healing complications have been observed in patients receiving sirolimus (SLR). This study examined the degree and duration of delayed healing in various protocols using SLR. Sprague-Dawley rats underwent a standard midline abdominal incision and wound closure. Groups of 6 rats each were randomized to receive different doses of SLR (2 and 5 mg/kg) with or without loading dose (10 mg/kg x3 days), and with or without steroids (20 mg/kg x3 days followed by 5 mg/kg for 2 weeks). Rats were humanely killed on postoperative days 5, 10, or 15. Wound breaking force was measured using the EHMI BIAX-II instrument and tensile strength was calculated. Wounds in control animals had gradual increase in tensile strength during the 15-day observation. In contrast, high and loading doses of SLR caused reduction in wound strength until day 10, but the wounds' tensile strength became equivalent to control by day 15. The addition of steroids prolonged wound recovery with low doses of SLR until day 15 and had very profound effects on healing in high-dose SLR-treated animals (>50% reduction) that continued beyond the 2 weeks of observation. Low doses of SLR in non-steroid-treated animals had a short-term (5-day) impact on wound healing; high dose and loading doses delayed healing for 10 to 15 days. The addition of steroids had a synergistic effect on delayed wound healing, particularly in animals receiving high-dose SLR, which demonstrated prolonged wound weakness. These results may provide practical guidelines for postoperative introduction of SLR in the context of various clinical protocols.

Phylogenetic and structural analyses of the oxa1 family of protein translocases.

Mitochondrial Oxa1p homologs have been shown to function in protein export and membrane insertion in bacteria, mitochondria and chloroplasts, but their mode of action, organismal distribution and evolutionary origins are poorly understood. All sequenced homologs of Oxa1p were retrieved from the databases and multiply aligned. All organisms with a fully sequenced genome possess at least one Oxa1p homolog showing that the family is truly ubiquitous. Most prokaryotes possess just one Oxa1p homolog, but several Gram-positive bacteria and one archaeon possess two, and eukaryotes may have as many as six. Although these proteins vary in length over a 5-fold range, they exhibit a common hydrophobic core region of about 200 residues. Multiple sequence alignments reveal conserved residues and provide the basis for structural and phylogenetic analyses that serve to characterize the Oxa1 family.

Increased expressions of CD69 and HLA-DR but not of CD25 or CD71 on endometrial T lymphocytes of nonpregnant women.

To investigate lymphocyte subpopulations and the status of T-cell activation at different phases of the menstrual cycle, lymphocytes in endometrial tissue were analyzed by dual-color flow cytometry in 39 patients. Compared with peripheral blood, the lymphocytes in the endometrium had a higher CD3-/(CD56+ or CD16+) ratio (25.2% +/- 6.8% vs 11.1% +/- 7.0%), but an inverted CD3+ CD8-/CD3+ CD8+ ratio (0.5 vs 1.8) and a minimal amount of B cells (3.3% +/- 3.1%). TcR gamma delta + T cells accounted for a minor proportion (7.8% +/- 5.1%) in endometrium. The proportions of TcR alpha beta + (85.0% +/- 6.6%) and CD3+ CD56+ (7.4% +/- 4.4%) endometrial T lymphocytes were found significantly different from those in peripheral blood (89.1% +/- 5.6% and 3.8% +/- 3.4%, respectively). As the endometrium proceeded from proliferative phase to luteal phase, the proportion of CD3+ CD8+ T cells in peripheral blood increased from 35.6% +/- 6.9% to 41.3% +/- 8.4% and CD3+ CD8- T cells decreased from 64.4% +/- 6.9% to 58.7% +/- 8.4%. The endometrial T cells expressed high levels of CD69 (84.1% +/- 18.9%) and DR (75.9% +/- 9.7%), but rarely expressed CD25 (7.0% +/- 5.4%) and CD71 (2.8% +/- 1.8%). The patterns of expression of these activation markers were similar in both proliferative and luteal phases. Our observations suggest that endometrial T lymphocytes are in a state of recent and persistent activation. Lymphocytes expressing the NK cell markers (CD56 or CD16) and CD8+ accounted for a significant proportion, suggesting that they may play important roles in local defense.

How many pulmonary alveoli are supplied by a single arteriole and drained by a single venule?

A detailed measurement of histological specimens of the lungs of the cat shows that each terminal precapillary vessel (arteriole) supplies, on the average, 24.5 pulmonary alveoli; each terminal postcapillary vessel (venule) drains, on the average, 17.8 alveoli. These numbers link pulmonary alveolar blood flow in capillary sheets with the flow in pulmonary arteries and veins which are cylindrical tubes. They are key numbers needed for hemodynamic analysis. In the literature, these numbers are variously speculated to be 1 or smaller; thus our results correct, even though only for the cat, an important concept.

Patency and compliance of pulmonary veins when airway pressure exceeds blood pressure.

Our measurements on cat's lung show that pulmonary veins and venules are not collapsible, but remain open when the alveolar gas pressure (PA) exceeds the local blood pressure (Pv). Their compliance constants show no discontinuity as Pv falls below PA. The capillaries, however, do collapse when PA greater than Pv. The explanation of the patency of the veins when PA greater than Pv is the pulling on the blood vessels by tension in the interalveolar septa. Photomicrographs show that each venule (or vein) is pulled radially by three or more interalveolar septa. Capillary sheets, however, are exposed to gas on the lateral sides and can readily collapse when PA greater than Pv. These facts provide the key to the analysis of pulmonary blood flow in zone 2. The "sluicing" gate, i.e., the site of flow limitation, must be located at the junctions of capillary sheets and the first generation of venules. Further, data on the branching pattern and compliance of small pulmonary veins, which are needed in quantitative analysis of pulmonary circulation, are presented.