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M M Faas

Publications and source records attributed to M M Faas.

29 records · Page 2Linked to original sources

Aspirin treatment of the low-dose-endotoxin-treated pregnant rat: pathophysiologic and immunohistologic aspects.

In the present study, we evaluated the effect of low-dose aspirin (acetylsalicylic acid (ASA); 1.0 mg/kg daily) on blood pressure, albumin excretion, glomerular fibrinogen deposits, and glomerular (basement) membrane-bound adenosine diphosphatase (ecto-ADPase) activity, as well as on glomerular inflammation in pregnant rats infused with low-dose endotoxin (1.0 mg/kg). Rats (day 14 of pregnancy) were infused with endotoxin (ET rats) or saline (control rats) and received ASA in their drinking water. These rats were compared with non-ASA-treated rats. Blood pressure and albumin excretion were measured from day 15 to day 21, and glomerular fibrinogen and ecto-ADPase activity were measured at day 21. Glomerular inflammation was evaluated at various times after the start of the infusion. The results show that treatment with ASA had a significant beneficial effect on hypertension and inflammation induced by endotoxin in pregnant rats, whereas it reduced albumin excretion and glomerular fibrinogen deposits in some of the rats.

Albuminuria↗

Reproductive condition and the low-dose endotoxin-induced inflammatory response in rats. Glomerular influx of inflammatory cells and expression of adhesion molecules.

These experiments were designed to study the increased sensitivity of pregnant rats to endotoxin. Pregnant (Pr), cyclic (C), and progesterone (P)-treated pseudopregnant rats with or without a decidualized uterus (PSP and DEC rats, respectively) received infusions of an ultra-low dose of endotoxin (1.0 microg/kg BW) and were killed 3 days later. Pr, PSP, and DEC rats were infused on Day 14, C rats on diestrus. Endotoxin-infused rats were compared with saline-infused rats in the same reproductive conditions. The inflammatory reaction of the glomeruli of the kidneys was studied by immunohistochemical methods using 4-microm cryostat sections stained with specific monoclonal antibodies against neutrophils (polymorphonuclear cells, PMNs) and monocytes (MOs), and against the adhesion molecules ICAM-1 and VCAM-1 on the endothelium, and LFA-1, MAC-1, and VLA-4 on the leukocytes. Endotoxin infusion increased glomerular PMN and MO number in Pr, PSP, and DEC rats, all of which have elevated P levels, but not in C rats, which do not. The endotoxin-induced expression of adhesion molecules, associated with this influx of inflammatory cells, varied with the reproductive condition. In C rats there was no increased adhesion molecule expression after endotoxin treatment, in Pr rats there was increased expression of both the combinations ICAM-1/LFA-1 and VCAM-1/VLA-4. DEC rats did not express either of these combinations (although there was expression of ICAM-1); PSP rats expressed the combination ICAM-1/MAC-1. Adhesion molecule expression thus seems to be regulated by ovarian (e.g., P) and placental factors (e.g., of trophoblastic and decidual origin). Because the different combinations of adhesion molecules in the various reproductive conditions after exposure to endotoxin led to more or less the same leukocyte influx under these conditions, the increased sensitivity to endotoxin of pregnant individuals cannot be reduced to differences in leukocyte influx into the glomeruli.

Animals↗

Modulation of glomerular ECTO-ADPase expression by oestradiol. A histochemical study.

The effect of 17-beta-oestradiol (OE2) upon the activity of the glomerular anti-thrombotic ecto-enzyme ADPase was studied in cyclic and ovariectomized (OVX) Wistar rats. On day 0 (i.e. at the time of ovariectomy or 11 days after ovariectomy) rats received OE2-releasing Silastic implants or empty implants and were sacrificed on day 3, 10 or 21. Cryostat kidney sections were histochemically stained for ecto-ADPase activity using enzyme-histochemistry and glomerular reaction product was quantitatively evaluated by computerized image analysis. Both the histological distribution of reaction product in each glomerulus, as reflected by the relative glomerular area covered with reaction product, as well as enzyme activity, as reflected by staining intensity of the reaction product, were scored. The results show significantly decreased histological distribution after OVX; OVX, however, did not change enzyme activity. It further appeared that OE2 (partly) prevented the decrease of histological distribution in OVX rats, while the enzyme activity was significantly increased by exogenous OE2. In cyclic rats, OE2 did not change histological distribution, although OE2 significantly increased enzyme activity in these rats. It is concluded that glomerular ecto-ADPase expression in the rat kidney is influenced by one or more ovarian factor(s), a very likely candidate being oestradiol. These results may thus point to a dual action of OE2 upon haemostasis: In addition to the known enhancement of procoagulatory plasma factors by OE2, also anti-aggregatory effects may be stimulated by OE2 as reflected by upregulation of vessel wall associated ecto-ADPase activity.

Analysis of Variance↗

The glomerular filtration rate during pregnancy: saline infusion enhances the glomerular filtration rate in the pregnant rat.

The glomerular filtration rate (GFR) of pregnant rats is generally believed to exceed non-pregnant values. This notion is primarily based upon standard insulin clearances. However, the insulin clearance requires continuous infusion of insulin usually dissolved in saline. Since saline infusion per se in pregnancy may influence the GFR, in the present study the effect of saline infusion upon the GFR in pregnant as compared with cyclic rats was investigated using various methods. The standard insulin clearance was compared using the standard 51Cr-EDTA method which does not require saline infusion. Clearance of insulin dissolved in glucose (5% in distilled water) instead of saline was also tested, while the 51Cr-EDTA method was employed using additional fluid infusion with either saline or 5% glucose in distilled water in an identical manner as compared with the insulin method. The GFR was also studied in conscious rats using 51Cr-EDTA clearance with and without fluid infusion. The distribution volume of 51Cr-EDTA was measured in nephrectomized rats (pregnant and cyclic) with and without saline or glucose infusions. The results show a significant increase of the GFR in pregnant rats as compared with cyclic rats only when saline was infused during the measurement; thus, GFR measurements without fluid infusion or replacement of saline by glucose during the measurements did not show a significant increase of GFR in pregnant rats. The volume of distribution per gram body weight of 51Cr-EDTA after saline infusion, but not after glucose infusion, was significantly increased as compared with the values obtained without additional infusion. It is concluded that the increase of the GFR seen in pregnant rats when either the 51Cr-EDTA method or the insulin method is accompanied by saline loading is rather due to infusion of saline in the pregnant animal and not a result of the pregnant condition per se.

Animals↗

Glomerular inflammation in pregnant rats after infusion of low dose endotoxin. An immunohistological study in experimental pre-eclampsia.

Increased endotoxin sensitivity during pregnancy occurs in many animals, including rats. The mechanism of this phenomenon is not understood. In the present study it was investigated whether this increased sensitivity is reflected by an altered inflammatory pattern. Inflammatory cell influx, the O2(-)-producing potential of these cells, and expression of adhesion molecules was studied in the glomeruli of pregnant and cyclic rats at various intervals after low dose endotoxin infusion. Kidney sections were stained for monocytes and adhesion molecules (ICAM-1, VCAM-1, LFA-1, and VLA-4) using monoclonals, while potentially O2(-)-producing neutrophils (ie, activated neutrophils) were quantified using immunohistochemical methods. The results show early glomerular influx of activated neutrophils, maximally 4 hours after endotoxin. Both absolute neutrophil counts and relative numbers of activated neutrophils were significantly increased in pregnant versus cyclic rats. In contrast to cyclic rats, showing transient monocyte influx, in pregnant endotoxin-treated rats monocyte influx reaches a maximum at t = 168 hours. These cell kinetics were paralleled by expression of the various adhesion molecules. It was concluded that pregnancy profoundly influences not only the inflammation kinetics after endotoxin, but also the violence of the reaction, reflected by activated neutrophils. This altered glomerular inflammatory pattern may help to explain why low dose endotoxin infusion induces pre-eclamptic-like symptoms (such as an intraglomerular prothrombotic microenvironment and proteinuria) exclusively in the pregnant rat.

Animals↗

A new animal model for human preeclampsia: ultra-low-dose endotoxin infusion in pregnant rats.

OBJECTIVE: An animal model for preeclampsia was developed by means of an ultra-low-dose endotoxin infusion protocol in conscious pregnant rats. STUDY DESIGN: Rats received a permanent jugular vein cannula on day 0 of pregnancy, through which endotoxin (1.0 micrograms/kg body weight) (n = 10) or saline solution (n = 6) was infused during 1 hour on day 14 of pregnancy. Blood pressure, albuminuria, and platelet counts were measured, and histopathologic studies was performed in these rats. RESULTS: A significant increase of blood pressure (p < 0.05) and of urinary albumin excretion (p < 0.05) was observed in endotoxin-treated pregnant animals, in contrast to control pregnant rats receiving saline solution. Platelet coagulopathy was found and glomerular fibrinogen deposits could be detected only in the endotoxin-treated pregnant rats. In addition, the activity of the glomerular antithrombotic enzyme adenosine diphosphatase was decreased in endotoxin-treated pregnant rats compared with saline solution-treated pregnant rats. CONCLUSION: Because histopathologic and clinical events in this model mimic predominant features of human preeclampsia, this model may enable further study into the pathophysiologic mechanisms of this complication of pregnancy.

Albuminuria↗

Reproductive condition, glomerular adenosine diphosphatase activity, and platelet aggregation in the rat: effect of endotoxin.

In experiment A, the activity of the glomerular antithrombotic enzyme adenosine diphosphatase (ADPase) and the sensitivity of this enzyme for endotoxin (1.0 microgram/kg BW) in various reproductive conditions of female rats were studied through use of enzyme histochemical methods. In experiment B, the effect of this dose of endotoxin on the thrombotic tendency of the glomeruli in pregnant (Pr) and pseudopregnant (PSP) rats was studied by means of ex vivo alternate perfusion of the kidneys with human platelets and adenosine diphosphate (ADP). In experiment A, cyclic (C), ovariectomized (OVX), Pr, and PSP rats were infused with endotoxin or saline. Three days later (for Pr and PSP rats, Day 8), animals were killed. In intact rats (C, Pr, PSP), the activity of glomerular ADPase was the same; however, the activity decreased after OVX. Endotoxin decreased the activity of glomerular ADPase in Pr rats only. In endotoxin-treated Pr rats, spontaneously formed platelet microaggregates were present in a few glomeruli; in glomeruli of the other groups, microaggregates were not observed. Platelet microaggregates were also present in the venous microvasculature of endotoxin-treated Pr rats and, to a lesser extent, in that of other groups, while saline-treated OVX rats were negative in this respect. In experiment B, Pr and PSP rats were treated as in experiment A; ex vivo kidney perfusion was performed on Day 8. Immediately after perfusion, rats were killed. Only Pr endotoxin-treated rats exhibited significantly increased intraglomerular platelet aggregation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Diphosphate↗

Regulation of peripheral glucagon concentrations in cyclic, pregnant, and lactating rats.

In the rat, peripheral glucagon concentrations were studied throughout pregnancy and lactation. Basal glucose concentrations were decreased during late pregnancy and during lactation, but basal glucagon concentrations were not affected. Infusion of glucose (7.4 mg/min) caused an elevation of the glucose concentrations, which became lower in the course of lactation, and a suppression of the glucagon concentrations which was the same throughout pregnancy and lactation. Ingestion of 336 mg of glucose or 1 g of rat chow throughout pregnancy and lactation induced a transient increase of the glucose concentrations and a biphasic glucagon response: following a short-lasting elevation, the glucagon concentrations became suppressed. The glucagon responses to these tests did not change during pregnancy and lactation. It is concluded that the regulation of the peripheral glucagon concentration is not affected by pregnancy or lactation, and that the response of the glucagon concentration to a metabolic challenge varies with the kind of test (oral or intravenous) used.

Animal Nutritional Physiological Phenomena↗

The increased endotoxin-sensitivity of pregnant rats, as reflected by glomerular ecto-ADP-ase activity, is not dependent on the presence of decidual cells.

In the present study the possible role of decidual cells in the pregnancy-associated increased sensitivity of glomerular ecto-ADP-ase to endotoxin was investigated. Early (day 5) pregnant (E-Pr; n = 10), pseudopregnant (E-PSP; n = 10), (day 5), pseudopregnant rats with a decidualized uterus (E-DEC; n - 10), as well as late (day 14) pregnant (L-Pr; n = 10), pseudopregnant (L-PSP: n = 10) (day 14), and pseudopregnant rats with a decidualized uterus (E-DEC; n = 10) were infused with either endotoxin (1.0 mg/kg bw) or saline. Three days later rats were killed and specimens of the left kidney were snap-frozen. Cryostat kidney sections (4 microns) were stained for ecto-ADP-ase activity and quantitatively evaluated. The results show that only glomerular ecto-ADP-ase activity of both groups of pregnant rats (E-Pr and L-Pr) was significantly decreased after endotoxin infusion as compared to saline infusion. In the other groups of rats, no significant differences in ecto-ADP-ase activity were observed between saline and endotoxin infusion. It is concluded that decidual cells do not play a role in the increased sensitivity of ecto-ADP-ase to endotoxin during pregnancy.

Analysis of Variance↗

The immunology of successful pregnancy.

Immune responses play an important role in various reproductive processes, including ovulation, menstruation and parturition. Clearly, during pregnancy, when the mother must accept a semi-allogeneic fetus, immune responses also play a very important role. This was first recognized by Medawar in 1953, when the concept of the fetal allograft was presented in order to explain the immunological relationship between mother and fetus. Since then, the immunology of pregnancy has been the leading subject within reproductive immunology research. Yet, the question of why the semi-allogeneic fetus is not rejected by the mother remains unresolved. The present review provides an update of current knowledge on the subject of the so-called 'immunological paradox of pregnancy'.

Female↗