| 1. |
|
|
| 2. |
|
|
| 3. |
- Löfgren, Mats
(author)
-
Progesterone in human parturition : progesterone and 5α-pregnane-3,20-dione in relation to human myometrial activity
- 1991
-
Doctoral thesis (other academic/artistic)abstract
- This study was undertaken to evaluate the relationship of progesterone and 5α-pregnane-3,20-dione (5αDHP), a major progesterone metabolite, to human parturition. The serum concentrations of 5αDHP prior to, during and following parturition were to be established, as well as its maternal and fetal concentration in different modes of delivery. Some of its effects in vitro were also to be studied. Progesterone was included primarily as a reference substance. 5α-pregnane-3α-ol-20-one (3αOH-DHP), a potent CNS depressant progesterone metabolite, was included in the in vitro study. Progesterone: The maternal serum concentration of progesterone is stable during the last three weeks of pregnancy preceding spontaneous labor and through labor. The various modes of delivery studied were elective cesarean section; ocytocin resistant fuctional dystocia; normal, effective, induced labor; and normal, effective, spontaneous labor. The serum progesterone concentrations in dystocia and at elective cesarean section were lower than during normal labor (P<0.005 - p<0.001). Women with ineffectual or no labor at all had progesterone concentrations ranging between 77 and 48% in maternal serum and for umbilical cord serum 65-43% of those at normal labor. In normal labor, primiparous women had higher progesterone concentrations than parous women. When scrutinizing the literature, similar results were found, though interpreted differently. In the in vitro model, human term myometrial muscle strips constantly exposed to progesterone started to contract later (p<0.005), but with a higher frequency (p<0.01) than parallel controls deprived of progesterone. A new property of progesterone emerges when these results are combined with findings in the literature regarding progesterone. Progesterone in high concentrations are related to normal, effective labor. 5α-pregnane-3,20-dione (5αDHP): Mean serum 5αDHP concentrations declined significantly during the last week of pregnancy (p<0.005). During labor, the maternal 5αDHP serum concentration remained stable. No distinct differences according to parity or mode of delivery were evident. The 5αDHP serum concentration in the fetal compartment was double that in the maternal compartment. 5αDHP had only minor effects in the in vitro model. These findings suggest a minor change in 5αDHP production preceding the onset of spontaneous labor, which could contribute to the increased progesterone concentration noted. 5α-pregnane-3α-ol-20-one (3αOH-DHP): No major effects of 3αOH-DHP were seen in the in vitro model. Thus unlikely that it hampers myometrial smooth muscle activity. In conclusion: Two generally accepted effects of progesterone in relation to parturition are; Decreasing concentrations induce labor while stable or increasing concentrations do have pregnancy maintaining properties. This study suggests a third property of progesterone in relation to human parturition. High and increasing progesterone concentrations seem to have uterotonic properties.
|
|
| 4. |
- Mincheva-Nilsson, Lucia
(author)
-
Immune cells in pregnant uterine mucosa : functional properties, cellular composition and tissue organization
- 1993
-
Doctoral thesis (other academic/artistic)abstract
- The pregnant uterus mucosa - decidua - is an "immunologically privileged" site. A semiallogeneic embryo is allowed to survive, develop, and grow while the same tissue implanted outside the uterus will be rejected. The decidua basalis, which participates in the placenta formation, is a tissue rich in lymphoid cells. We have studied decidua associated mononuclear cells (DMC) from normal early pregnancies in humans. The cells were investigated with respect to surface marker profiles, ultrastructure, organization in the tissue, and functional properties. In addition, we have studied the expression of receptors for the iron-binding protein lactoferrin on these cells, and characterized the receptor (Lf-R).Ten to fiftee percent of all cells in decidua belong to the lymphoid cell lineage. They are present in aggregates [lymphoid cell clusters (LCC) mainly located in the vicinity of decidual/endometrial glands] and as individual cells, intra- or subepithelially along the glands (IEL) , and in the stroma. The LCC appear to be centres of immune reactivity. They occur at a frequency of 0.40.2/mm2 tissue and are composed of different population of activated T cells and NK cells in close contact with each other. Interestingly, B cells are not present in the LCC. DMC consist of four major lymphocyte subpopulation of similar sizes: TCRγδ+/CD56+cells, TCRγδ+/CD56-cells, TCRγδ-/CD56+cells and TCRαβ+/CD8+cells. TCRαβ+/CD4+ cells and monocytes are also present. Most DMC have long, thick processes, microvilli, and cytoplasmic granules. They are in intimate contact with surrounding lymphoid, epithelial and stromal cells. Signs of cellular movement and excretion of granules are also seen.About half of the T cells are TCRαβ cells. These cells lack CD4 and CD8. A large fraction of them are CD56+, a rare phenotype at other sites. Most of the TCRγδ+ cells express activation/memory markers (CD45RO, the Kp43 antigen, transferrin receptor, and MHC class II antigens), and many cells express the mucosa homing receptor HML-1. Morphologically these cells either display features characteristic for cytotoxic cells or contain unique nuclear inclusions.More than half of TCRαβ cells are CD8+, but CD4+ cells are also found. These cells also display activation markers.DMC use both transferrin and lactoferrin for their iron supply. The Lf-R on activated lymphocytes appears to be made of two peptides of 47 and 65 kD MW.Freshly isolated DMC respond poorly or not at all to activation through the TCR/CD3 complex, probably due to the low surface density of the complex. However, the TCR/CD3 complex can be up-regulated by stimulation with PMA/Ionomycin in vitro, suggesting that the lymphocytes are suppressed in vivo. Glandular epithelial cells produce immunosuppressive factor(s) that act on CD8+, TCRγδ+, and CD56+ cells. The proximity between the LCC and the glands indicates that this factor(s) may play a role in local immunosuppression. The identity of the factor(s) is presently unknown. The cytokine mRNA profile of DMC, as determined by RT-PCR, reveals IFN-γ, IL-8 and TGF-β1 mRNA in all samples, and IL-1β, IL-2, IL-10, TNF-α and GM-CSF mRNA in some samples. The cytokine profile is compatible with down-regulation of CTL activity.The demands on the immune system in pregnant uterus mucosa are unique. On one hand, a genetically incompatible fetus must be accepted, the development of the placenta must be allowed, and the uteral mucosal tissue must be remodelled. On the other hand, the invasiveness of the trophoblast must be controlled, and the fetomaternal unit must be protected against infections. Our studies indicate that this is achieved through a highly regulated process involving different types of activated lymphoid cells interacting with each other and with glandular epithelial cells.
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
- Lindahl, Olof
(author)
-
The impression technique for assessment of tissue oedema : instrumentation, evaluation and applications
- 1993
-
Doctoral thesis (other academic/artistic)abstract
- An instrument for clinical noninvasive assessment of tissue oedema based on an impression method was developed. The method measures and evaluates the decaying force, due to translocation of tissue fluid, during mechanical compression of any site of tissue. We applied the impression method on physical models, animal models, and patients. Significant parameters for the assessment of tissue oedema that estimated tissue fluid translocation and tissue pressure could be derived from the registered impression force curves.Accuracy was determined theoretically and reproducibility was estimated on plastic foam. We described the clinical procedure for the instrument, and preliminary results from patients with chronic pitting oedema showed that the instrument detected larger fluid translocation on oedematous sites than on non-oedematous sites. We concluded that the instrument was acceptable for accurate measurements on biological tissue.Evaluation was performed in a rat testis model in which testicular interstitial fluid volume could be changed both artificially by 30-min infusions of different fluids with different fluid resistance properties, and pharmacologically by administration of hormones. We found that tissue pressure increased with infused fluid volume, and changes as small as 16 μl (7 % of total testis interstitial fluid volume) could be detected. Fluid translocation changed depending upon the infused fluid's resistance properties. Hormone-induced changes in rat-testis oedema altered both fluid translocation and tissue pressure. Discrete changes in vascular permeability were monitored.Investigation of generalised oedema in patients suffering from burn injury showed that tissue fluid translocation increased up to a maximum value after 6 days postburn and declined thereafter. We found tissue pressure to be relatively high during the first 7 days postburn as compared with 3-week postburn values. Force curve analysis suggested a flux of water-like fluid from the vasculature to the interstitial space during the first 6 days postburn. The course of postburn tissue swelling could be followed and estimated with the impression technique.Comparison with a new tactile sensor that measured physical properties of soft tissue showed that both methods detected changes in silicone hardness/softness and in hormone-induced changes of rat-testis interstitial fluid. We concluded that impression force estimated hardness of soft tissue, which can be helpful when investigating hardness of oedematous tissue.
|
|
| 9. |
|
|
