Challenges in Treating COVID-19 Patients With Severe Burn Injuries.

Here we present a case report of a young female patient with severe burn injury inflicting 27% of total body surface area (TBSA) associated with COVID-19 infection. Upon admission, Acinetobacter spp. (sensitive only to Colistin) was isolated from the wound swabs of the right arm, hand and thorax. On the fifth day after admission, a surgical excision was performed and 12% of TBSA was covered with homotransplants. The following day the patient had a sudden drop in oxygen saturation with hypotension (85/45 mmHg). Additionally, agitation, visual and auditory hallucinations were noticed. We found a massive pleural effusion on the left side and pneumonic foci on the right side. On the thirteenth day after admission the final surgical excision and homotransplantation of the skin were performed. In the following days, debridement of all necrotic tissue and covering of all the burned areas with homotransplants were done. Hemodynamic instability of the patient progressed along with the finding on the chest radiography, despite the local finding including adherent homotransplants with no signs of lysis or local infection at the wound beds. Due to low oxygen saturation, the patient was intubated on the fourteenth day after admission. Despite the measures taken, the lethal outcome occurred on the twenty-fifth day after admission to our Clinic. A decision on the right timing for surgical treatment in severely burned COVID-19 patients needs to be investigated in order to enable surgeons to make evidence-based decisions during the pandemic.

Nous présentons le cas d'une femme jeune souffrant d'une brûlure sur 27% SCT associée à une infection à COVID-19. À son entrée, elle était colonisée (zones brûlées du bras droit, de la main et du thorax) à Acinetobacter sensible uniquement à la Colistine. À J5 était réalisée une excision/homogreffe sur 12% SCT. Le lendemain survenaient brutalement un collapsus (PA 85/45 mm Hg) et une hypoxie profonde. Elle était agitée et souffrait d'hallucinations visuelles et auditives. Il existait un épanchement pleural gauche de grande abondance et une foyer de pneumopathie à droite. Elle a dû être intubée à J14. À J15, l'excision/homogreffe a été complétée. Elle était reprise le lendemain pour complément d'excision et reprise des homogreffes. L'instabilité hémodynamique et les signes radiographiques s'aggravaient quand les homogreffes ne lysaient pas. Elle est décédée à J25. Le positionnement temporel de l'excision chez les patients brûlés atteints de COVID-19 doit être mûrement réfléchi.

The Impact of the COVID-19 Pandemic on Self-Inflicted Burn Injuries in Patients With Previously Diagnosed Bipolar Disorder.

Here we present a case of a 52-year-old female patient who was admitted to the Clinic in December 2021 due to the presence of right side facial burns which were caused by a cigarette lighter under suspicious conditions. Her past medical history revealed she was diagnosed with bipolar disorder at the age of 20 and was hospitalized multiple times for the treatment of manic episodes. The last psychiatric hospitalization took place in October 2021. She had deep second-degree burns on the right side of the face, head and neck, with a total body surface area involvement of approximately 3%. On hospital day 18, she was found unresponsive, dyspnoic, with no palpable pulse and measurable tension. Electrocardiogram (ECG) monitoring revealed sinus bradycardia followed by cardiac asystole. After the first few minutes of cardiopulmonary resuscitation, heart and lung action was re-established. Due to the presence of ECG changes in the form of ST depression and negative T waves in V2-V6, D1 and aVL, also higher blood level of high sensitivity troponin T, she was urgently transported to the Coronary Unit where she was diagnosed with non-ST-elevation myocardial infarction. On hospital day 27, due to the presence of sub-febrile temperature and non-productive cough, she was tested for COVID-19 infection and transported to the COVID Hospital Batajnica. She was discharged with stable laboratory parameters and normal chest radiography 37 days following initial admission. Considering the great psychological impact related to the COVID-19 pandemic, extensive mental health support and regular monitoring of critical groups is indicated.

Nous présentons le cas d'une femme de 52 ans hospitalisée en décembre 2021 pour brûlures par briquet de la partie droite du visage, survenue dans des circonstances suspectes. Le diagnostic de trouble bipolaire avait été posé sur elle à l'âge de 20 ans et elle a été hospitalisée à de multiples reprises en raison d'épisodes maniaques, la dernière fois en octobre 2021. Les brûlures, profondes, siégeaient au niveau de la partie droite du cou, du visage et du cuir chevelu, représentant 3% de sa SCT. À j18, elle est retrouvée inconsciente, dyspnéique, sans pouls palpable ni pression artérielle mesurable. L'ECG montre une bradycardie sinusale puis une asystole. Le ressuscitation est un succès en quelques minutes. On observe un sous-décalage de ST en D1, aVL et de V2 à V6 ainsi qu'un mouvement de troponine motivant son transfert en cardiologie, où le diagnostic d'infarctus du myocarde est posé. A J27, le diagnostic d'infection à COVID-19 est avéré, à la suite d'un syndrome fébrile et d'une toux sèche, elle est transférée à l'hôpital Batajnica. Elle sort à J37, avec une biologie et une radiographie thoracique normales. En raison des conséquences psychologiques de la pandémie COVID-19, un support psychologique doit pouvoir être largement disponible et les populations les plus à risque doivent être régulièrement suivies.

Voxel model of a rabbit: assessment of absorbed doses in organs after CT examination performed by two different protocols.

The objective of this work was to assess absorbed doses in organs and tissues of a rabbit, following computed tomography (CT) examinations, using a dedicated 3D voxel model. Absorbed doses in relevant organs were calculated using the MCNP5 Monte Carlo software. Calculations were perfomed for two standard CT protocols, using tube voltages of 110 kVp and 130 kVp. Absorbed doses were calculated in 11 organs and tissues, i.e., skin, bones, brain, muscles, heart, lungs, liver, spleen, kidney, testicles, and fat tissue. The doses ranged from 15.3 to 28.3 mGy, and from 40.2 to 74.3 mGy, in the two investigated protocols. The organs that received the highest dose were bones and kidneys. In contrast, brain and spleen were organs that received the smallest doses. Doses in organs which are stretched along the body did not change significantly with distance. On the other hand, doses in organs which are localized in the body showed maximums and minimums. Using the voxel model, it is possible to calculate the dose distribution in the rabbit's body after CT scans, and study the potential biological effects of CT doses in certain organs. The voxel model presented in this work can be used to calculated doses in all radiation experiments in which rabbits are used as experimental animals.

The onset of ulcerative colitis upon Helicobacter pylori eradication in a 72-year-old woman: report of a rare case with a 3-year follow-up.

BACKGROUND: Epidemiological studies suggest an inverse association between H. pylori infection/exposure and inflammatory bowel disease prevalence/incidence, however, there are no reports of individual patients who developed a "non-transient" ulcerative colitis (UC) following H. pylori eradication. CASE PRESENTATION: We report a case of a 72-year-old female with an elderly-onset UC developed upon H. pylori eradication and a 3-year follow-up of the progression to steroid-dependent colitis complicated with enteropathic arthritis and final containment of the disease with golimumab. In our patient, H. pylori eradication was associated with the development of pancolitis that evolved into clinically, endoscopically, and pathohistologically confirmed UC. CONCLUSIONS: The case of our patient provides a unique clinical context for a growing body of literature suggesting molecular mechanisms involved in the interaction of genes, environment, and microbiota to be of critical importance in the etiopathogenesis of UC, and thus, provides a valuable set of complementary translational information for preclinical and epidemiological research on the topic.

Low Dose Aspirin in high-risk pregnancies: The volatile effect of acetylsalicylic acid on the inhibition of platelets uncovered by G. Born's light transmission aggregometry.

Preeclampsia still represents a life-threatening pregnancy complication, associated with severe maternal and neonatal morbidity and mortality. Low-dose Aspirin is advised to avoid preeclampsia in high-risk pregnancies worldwide. As Aspirin does not cover all women at risk, the prescription raises questions concerning optimal target population, dosage, and onset of therapy. The aim of this study was to test platelet responsiveness on Aspirin by optical aggegrometry, to gain robust biochemically assessment data of Aspirin in an obstetric cohort. 248 women at high risk for development of preeclampsia were included in the study. Aspirin-prophylaxis was administered either in 100 mg (n = 229) or 150 mg (n = 90) daily. Dosing of 100 mg Aspirin was maintained if testing revealed a sufficient platelet inhibition. If platelet inhibition was insufficient, dosage was increased to 150 mg Aspirin and re-testing was advised. 91 patients (91/229 = 39.7%) presented a sufficient inhibitory Aspirin effect at a dosage of 100 mg, but in 138 patients LTA showed an inadequate Aspirin response (138/229 = 60.3%). In 19 women 150 mg Aspirin was administered as starting dose due to new recommendations. Of all women at 150 mg Aspirin 64 did not properly respond (35.4%). The overall rate of sufficient responding women regardless the Aspirin dose was 64.6%. This study demonstrates still an insufficient inhibition of platelet aggregation in about 1/3 of women even with a dosage of 150 mg Aspirin daily, who might potentially benefit from further increase. These data show, that there is a need for further research to allow a personalized approach for individualized Aspirin therapy, maximizing the preventive benefit for mother and child.

Effects of cinchonine, a Cinchona bark alkaloid, on spontaneous and induced rat ileum contractions.

AIM: Quinine, a frequently used anti-malaria alkaloid isolated from the Cinchona bark, possesses numerous toxic properties, the majority of which arrive from a dysfunction of the gastrointestinal tract. Similarly, cinchonine, another alkaloid from the Cinchona bark, displays a great potential for treating malaria (especially the resistant forms). METHODS: In this work, we aimed to evaluate the effects of cinchonine on spontaneous and induced Wistar rat ileum contractions in order to uncover potential side effects that might arise after its application. RESULTS: Cinchonine produced a concentration-dependent spasmolytic activity, which was found to be reversible (i.e. disappeared after tissue wash-up), with an IC50 value of 273 µM. Furthermore, the mechanism of action of cinchonine at IC50 elucidated through experiments with acetylcholine and Ca2+-induced ileum contractions. The applied IC50 concentration of cinchonine statistically significantly prevented the occurrence of contractions after the application of specific agonist. The obtained results are in a range with the effects seen with standard receptor antagonists, i.e. atropine and verapamil. CONCLUSIONS: The obtained results showed that cinchonine inhibited both types of induced contractions, suggesting a Ca2+-channels mediated modus operandi (Fig. 4, Ref. 19).

Temporal changes of the endothelin system in human cytotrophoblasts during the first trimester of pregnancy.

The first trimester of pregnancy is characterized by continuous proliferation, invasion and differentiation of cytotrophoblasts. These processes are precisely controlled both, in space and time by molecules such as endothelin-1 (ET-1). ET-1 is expressed in human first trimester trophoblast and is known to stimulate cytotrophoblast proliferation through endothelin A and B receptor subtypes (ET(A) and ET(B)), and cytotrophoblast invasion through ET(B). However, temporal changes of the ET system during the first trimester of pregnancy have not been previously studied. This study tested the hypothesis that ET-1 release, ET(A) and ET(B) expression are increased towards the end of the first trimester of pregnancy (weeks 10-12 vs. weeks 6-9), resulting in increased cytotrophoblast proliferation and invasion. Tissue samples were obtained from 17 surgical pregnancy interruptions (week 6-9: n=9; week 10-12: n=8). After cytotrophoblast isolation, the invasive and proliferative phenotypes were immune-separated by an alpha(6)-integrin antibody. Both proliferative and invasive cytotrophoblasts were cultured separately on plastic or Matrigel for 24 h. ET-1 release into the culture medium of both cytotrophoblast subtypes was measured by radioimmunoassay. ET(A) and ET(B) mRNA expression was measured by RT-PCR, and the ET-1 effect on cytotrophoblast proliferation and invasion was determined using proliferation and invasion assays, respectively. ET-1 release increased from early to late first trimester of pregnancy in both proliferative (1.8-4.5 fold) and invasive cytotrophoblasts (9.3-28 fold), especially when cultured on Matrigel. This was paralleled by less ET(B) mRNA on invasive cytotrophoblasts independent of the time period in first trimester, whereas ET(A) expression was similar on proliferative an invasive cytotrophoblasts. Proliferation and invasion of cytotrophoblasts under control conditions decreased from early to late first trimester. ET-1 stimulated both processes at both periods with the most pronounced effect (7-fold) on invasion in late first trimester. The ET-1/ET-receptor system changes between weeks 6-9 and 10-12 in pregnancy. Our data suggest an autocrine and endocrine ET-1 effect, which is stronger in late than in early first trimester of pregnancy paralleled by different stimulatory effects on trophoblast invasion and proliferation. In general, this suggests time as an additional effector of the critical processes governing placental development in the first trimester of human pregnancy.

The significance of structured parental educational intervention on childhood atopic dermatitis: a randomized controlled trial.

BACKGROUND: Parental education is important in managing childhood chronic diseases. OBJECTIVES: The aim of the study was to evaluate the effects of a short-term structured educational programme for parents of children with moderate to severe atopic dermatitis ( AD), aged 3 months to 7 years, on the clinical course of AD, parental stress, anxiety and the quality of family life. METHODS: One hundred thirty-four parents with AD children were recruited in a randomized controlled clinical trial at the Outpatient Unit of Pediatric Dermatology, Children's Hospital in Zagreb. The primary outcome was change in the severity of eczema measured using SCORing AD (SCORAD) and Patient Oriented (PO) SCORAD index, changes of symptom scores for pruritus and sleep disturbance. Secondary outcomes included change in stress level according to the Perceived Stress Scale (PSS); change in anxiety level according to State Trait Anxiety Inventory (STAI) and change in the quality of family life according to the Croatian version of the Family Dermatology Life Quality Index (FDLQI). RESULTS: Participants in the intervention group had a significantly lower SCORAD (P = 0.000), PO SCORAD (P = 0.000) index, pruritus (P = 0.000), sleep disturbance (P = 0.001), level of perceived stress (P = 0.024) and anxiety as a state (P = 0.42) than those in the control group at the second visit. After the educational programme, participants in the intervention group had a significantly lower impact of AD on the total quality of family life (P = 0.006). We found a statistically significant difference between the two groups with respect to additional education received between the visits. The control group had acquired significantly more additional education (P = 0.007). There was no significant difference between groups in the amount of corticosteroid used. CONCLUSION: Our structured educational programme had a positive effect on AD severity, quality of family life, parental stress and anxiety.

Fructose-Rich Diet-Induced Changes in the Expression of the Renin Angiotensin System Molecules in the Heart of Ovariectomized Female Rats Could be Reversed by Estradiol.

The renin-angiotensin system has been implicated in the development of metabolic syndrome and appears to be a key in the local tissue control of normal cardiac functions. Physiological concentrations of estrogens have been shown to be cardioprotective, especially against the damaging effects of fructose-rich diet. The aim of the study was to investigate the expression of the renin-angiotensin system molecules with potentially deleterious effect on the heart (angiotensin-converting enzyme and angiotensin II type 1 receptor) and those with potentially protective effects, (angiotensin-converting enzyme 2 and angiotensin II type 2 receptor), in ovariectomized fructose fed female rats with 17ß-estradiol replacement. Real-time PCR and Western blot analysis were used for quantification of gene and protein expression in the heart. Fructose diet increased the expression of angiotensin-converting enzyme and angiotensin II type 1 receptor and decreased the expression of angiotensin-converting enzyme 2 and angiotensin II type 2 receptor. On the other hand, estradiol replacement seems to undo fructose diet effects on cardiac renin-angiotensin system. Downregulation of angiotensin-converting enzyme and angiotensin II type 1 receptor, and reversion of expression of both potentially protective molecules, angiotensin-converting enzyme 2 and angiotensin II type 2 receptor, to the control level in cardiac tissue took place. Obtained results suggest that estradiol may reverse the harmful effect of fructose-rich diet on the expression of renin-angiotensin system molecules. These findings may also be important in further research of phenotypes like insulin resistance, metabolic syndrome, and following cardiovascular pathology in females.

Oestradiol Treatment Counteracts the Effect of Fructose-Rich Diet on Matrix Metalloproteinase 9 Expression and NFκB Activation.

Fructose-rich diet induces metabolic changes similar to those observed in metabolic syndrome. Among other matrix metalloproteinases, MMP-9 has an important role in adverse cardiac remodelling and might have a role in the development of cardiovascular disorders associated with metabolic syndrome. The changes of MMP-9 expression could be mediated via the NFκB pathway. In this study we investigated the effect of fructose-rich diet on MMP-9 expression in the heart of male and female rats, along with the effect of fructose-rich diet and oestradiol on MMP-9 expression in ovariectomized females. We further assessed the effect of fructose-rich diet and oestradiol on NFκB activation, measured as the level of p65 phosphorylation at Ser 276. The results showed that the diet regime did not affect the heart mass. Higher MMP-9 gene expression was found in cardiac tissue of male rats fed the fructose-rich diet than in females on the same diet regime. In ovariectomized females, fructose-rich diet upregulated MMP-9 protein and mRNA expression in the heart, as well as phosphorylation of the p65 subunit of NFκB at Ser 276. Oestradiol replacement therapy reverted these changes in the heart of ovariectomized females. This study has shown that oestradiol could revert the early molecular changes in MMP-9 expression induced by fructose-rich diet that occurred before cardiac hypertrophy development by decreasing phosphorylation of the NFκB p65 subunit at Ser 276.

Methylenetetrahydrofolate reductase gene variants and antipsychotic-induced weight gain and metabolic disturbances.

Weight gain and metabolic disturbances represent serious side-effects in antipsychotic (AP) treatment, particularly with clozapine and olanzapine. The methylenetetrahydrofolate reductase (MTHFR) gene is a key determinant in the folate metabolism and previous studies reported a significant effect on AP-induced weight gain and related metabolic abnormalities. Thus, we investigated MTHFR gene variants and changes in several important metabolic parameters in AP-treated patients. In this study, two functional MTHFR polymorphisms, rs1801133 (C677T) and rs1801131 (A1298C), were investigated for changes in weight and metabolic parameters. Genotypic associations were evaluated in a large population (n = 347 including 66 first episode psychosis, FEP patients) treated mostly with clozapine and olanzapine. We did not detect any genotypic association with weight changes (p > 0.05) in our total sample and in the sample refined for ancestry and medication. In our allelic analyses, we observed a trend for the 677-C allele to be associated with weight gain in the total sample (p = 0.03). This effect appeared to be driven by the FEP patients where those carrying the C-allele gained, on average, twice as much weight. Exploratory analyses revealed a significant association between the C677T and the A1298C polymorphism with HDL cholesterol serum levels in patients (p = 0.031). Overall we did not detect a major effect of two functional MTHFR gene variants and AP-induced weight gain. However, our findings suggest an effect of the C677T polymorphism in FEP patients and changes in weight and cholesterol levels. Further investigations in a larger sample are required.

New ischemic brain lesions on diffusion-weighted MRI after carotid artery stenting with filter protection: frequency and relationship with plaque morphology.

BACKGROUND AND PURPOSE: CAS carries an inherent risk of distal cerebral embolization, precipitating new brain ischemic lesions and neurologic symptoms. Our purpose was to evaluate the frequency of new ischemic lesions found on DWI after protected CAS placement and to determine its association with plaque morphology. MATERIALS AND METHODS: Fifty patients (mean age 65.13 ± 7.08 years) with moderate and severe internal carotid artery stenosis underwent CAS with distal filter protection. Fibrolipid and fibrocalcified plaque morphology was determined by sonography according to the relative contribution of echogenic and echolucent material, and by multisection CT using plaque attenuation. There were 46.81% of patients with fibrolipid and 53.19% with fibrocalcified plaques. DWI was performed before and 24 hours after CAS. RESULTS: Seven (14.89%) patients showed new lesions. Four (8.51%) had 6 new lesions inside the treated vascular territory. Three had a single lesion and 1 patient had 3 lesions (mean: 1.5 ± 1). Most lesions (66.66%) were subcortical, with a mean diameter of 9 mm (range 5-15 mm). All lesions occurred in the area supplied by the middle cerebral artery and were clinically silent. A significant relationship was found between plaque morphology and the appearance of new lesions. Patients with fibrolipid plaques had a significantly higher number of new lesions compared with patients with fibrocalcified plaques (P = .041). The absolute risk of new lesions in the fibrolipid group was 18.18%. CONCLUSIONS: New ischemic lesions were observed in the treated vascular territory in 8.51% of patients. The appearance of new ischemic lesions was significantly related to the plaque morphology. Fibrolipid plaques were associated with higher numbers of new lesions.

Sun behaviour patterns and perception of illness among melanoma patients.

BACKGROUND: Melanoma is one of the most aggressive skin tumours for which the major risk factor is ultraviolet radiation. Sun protection is extremely important, especially for melanoma patients who, once diagnosed with melanoma, have 500 times greater chance of developing another melanoma than the general population. OBJECTIVE: In this study, we examined the perception of melanoma and attitudes towards sun protection among melanoma patients and compared their results with the patients suffering from other dermatological disorders. METHODS: In total, 240 participants were included in the study: 120 patients suffering from melanoma and 120 participants in the control group. The Sun Behaviour Patterns Questionnaire and the Brief Illness Perceptions Questionnaire were used in this study to assess sun behaviours and perception of melanoma. RESULTS: Melanoma patients have negative attitude towards sunbathing: 57% avoid sunbathing and 27% spend time in the sun only during swimming, otherwise seeking shade, whereas participants in the control group have more positive attitude towards sunbathing. Results indicate very short time of using sunscreen protection during the year and very small number of people using adequate SPF value, in both melanoma and control group. CONCLUSION: Participants in control group perceive melanoma as a more serious illness than patients who think that melanoma has mild symptoms, is easy to cure and control, has moderate consequences and lasts relatively long. Both melanoma patients and participants in the control group show relatively good sun behaviour patterns and slightly negative attitudes towards sun protection.

PP068. Catastrophic antiphospholipid-syndrome (CAPS) - A severe pregnancy complication.

INTRODUCTION: Antiphospholipid syndrome (APS), is an autoimmune, hypercoagulable state caused by antibodies against cell-membrane phospholipids provoking arterial and venous thromboses as well as pregnancy-related complications such as miscarriage, stillbirth, preterm delivery, or severe preeclampsia. The syndrome occurs due to the autoimmune production of antibodies against phospholipid (aPL), a cell membrane substance. In particular, the disease is characterised by antibodies against cardiolipin (anti-cardiolipin antibodies) and ß2 glycoprotein I. In rare cases, APS can lead to rapid organ failure due to generalised thrombosis. This life-threatening complication is termed "catastrophic antiphospholipid syndrome" (CAPS) and is associated with a high maternal mortality. OBJECTIVES: To describe the characteristics of patients who developed catastrophic APS triggered during pregnancy and to possibly identify potential risk factors for the development of this complication. METHODS: Patients charts of women with autoimmune disorders (such as APS or systemic lupus erythematodes) observed and treated at the University of Graz and The University of Jena between 2007 and 2012 were evaluated. RESULTS: Four cases of CAPS were identified. In all women CAPS occurred as a severe early onset complication (<34 weeks of gestation) and all women had to be delivered by caesarean section between 27 and 32 weeks. With an "individualized" treatment including plasmapheresis, pregnancy can be prolonged for a short period to at least achieve lung maturation by steroids. Several specific features could be found: HELLP (haemolysis, elevated liver enzymes, low platelets) syndrome-like symptoms, eclampsia-like symptoms (headache, amaurosis), abdominal pain resistent to conventional analgesic therapy, and intrauterine growth restriction. Histologic examination after delivery revealed placental infarctions. CONCLUSION: It is important to consider the possibility of the development of catastrophic APS in those patients with signs of HELLP syndrome and multiorgan failure during pregnancy or puerperium, especially in those patients with previous history of abortions and/or thrombosis. In specialised centers prolongation of pregnancy with an individualized treatment including plasmapheresis may be an option.

Endothelin-1 stimulates proliferation of first-trimester trophoblasts via the A- and B-type receptor and invasion via the B-type receptor.

CONTEXT: Endothelin-1 (ET-1) stimulates proliferation and invasion of first-trimester human trophoblast cells. OBJECTIVE: To test the hypothesis that ET-1 effects are mediated by different receptor subtypes [ET receptor (ETR)-A and ETR-B]. DESIGN: The location of ETR in trophoblast cell columns (wk 6-12) was investigated by immunohistochemistry and autoradiography. Trophoblasts were isolated from first-trimester human placentas and proliferative and invasive subpopulations separated using an integrin α6 antibody. Cells were incubated for 24 h with 10 µm ET-1 and different ETR antagonists: PD142893 (unselective), BQ-610 (ETR-A), and RES-701-1 (ETR-B). After ETR down-regulation by antisense oligonucleotides, proliferation (thymidine incorporation, protein synthesis) and invasion (Matrigel invasion) were measured. ETR expression in isolated cells was analyzed by Western blotting and semiquantitative RT-PCR. RESULTS: Both ETR are expressed in both subpopulations in the cell column with predominance of ETR-A in the proximal part and proliferative subpopulation, whereas ETR-B is present at similar levels in both subpopulations. These results were confirmed at the mRNA level. ET-1 increased proliferation (maximum 267% of control) and invasion (maximum 288% of control) of first-trimester trophoblasts. The mitogenic ET-1 effect was inhibited (P < 0.05) by 40-80% with each receptor antagonist and by 44 and 40%, respectively, by ETR-A and ETR-B antisense oligonucleotides. The invasion-promoting effect was almost completely blocked in the presence of the ETR-B antagonists. CONCLUSION: The effect of ET-1 on cell proliferation in first-trimester trophoblasts is mediated by both ETR, whereas its effect on invasion is mediated predominantly by ETR-B. These effects are in line with the receptor subtype location.