Search PubMed⌕ Search

Biomedical subjects

Peter Husslein

Publications and source records attributed to Peter Husslein.

46 records · Page 3Linked to original sources
PubMed2002

Simvastatin reduces expression of cytokines interleukin-6, interleukin-8, and monocyte chemoattractant protein-1 in circulating monocytes from hypercholesterolemic patients.

OBJECTIVE: A number of studies have shown that statins decrease morbidity and mortality in patients with cardiovascular diseases. The anti-inflammatory effects of statins have recently been implicated in the clinical benefit that can be obtained in the treatment of atherosclerosis. Little is known about the mechanisms by which statins counteract inflammation. METHODS AND RESULTS: In this study, we asked whether simvastatin can influence in vitro and in vivo production of the proinflammatory cytokines interleukin (IL)-6, IL-8, and monocyte chemoattractant protein-1. A total of 107 hypercholesterolemic patients were treated with simvastatin. As measured by ELISA, serum levels of cytokines significantly decreased after 6 weeks of treatment (P<0.05). Furthermore, simvastatin decreased the expression of IL-6, IL-8, and monocyte chemoattractant protein-1 mRNA in peripheral blood mononuclear cells. Similar results were obtained in vitro by using cultured human umbilical vein endothelial cells and peripheral blood mononuclear cells from healthy normolipemic donors. Exposure to simvastatin, atorvastatin, or cerivastatin caused downregulation of the expression of cytokine mRNA in a time- and dose-dependent manner. Furthermore, all statins tested were able to reduce the concentrations of cytokines in cellular and extracellular fractions of human umbilical vein endothelial cells (P<0.05). CONCLUSIONS: Our data show that simvastatin is anti-inflammatory through the downregulation of cytokines in the endothelium and leukocytes. These effects may explain some of the clinical benefits of these drugs in the treatment of atherosclerosis.

Aged↗
PubMed2002

Human Hand1 basic helix-loop-helix (bHLH) protein: extra-embryonic expression pattern, interaction partners and identification of its transcriptional repressor domains.

The basic helix-loop-helix (bHLH) transcription factor, Hand1, plays an important role in the development of the murine extra-embryonic trophoblast cell lineage. In the present study, we have analysed the expression of Hand1 in human extra-embryonic cell types and determined its binding specificity and transcriptional activity upon interaction with different class A bHLH factors. Northern blotting and in situ hybridization showed that Hand1 mRNA is specifically expressed in amnion cells at different stages of gestation. Accordingly, we demonstrate that the protein is exclusively produced in the amniotic epithelium in vivo and in purified amnion cells in vitro using a novel polyclonal Hand1 antiserum. Reverse transcriptase-PCR and immunohistochemical staining of blastocysts revealed the production of Hand1 mRNA and polypeptide in the trophectodermal cell layer. In the presence of E12/E47, Hand1 stimulated the transcription of luciferase reporters harbouring degenerate E-boxes, suggesting that E-proteins are potential dimerization partners in trophoblastic tumour and amnion cells. In contrast, Hand1 diminished E12/E47-dependent transcription of reporters containing perfect E-boxes by inhibiting the interaction of Hand1/E-protein heterodimers with the palindromic cognate sequence. Furthermore, we show that Hand1 down-regulated GAL-E12-dependent reporter expression, indicating that the protein can also act directly as a transcriptional repressor. Mutational analyses of GAL-Hand1 suggested that two protein regions located within its N-terminal portion mainly confer the repressing activity. In conclusion, human Hand1 may play an important role in the differentiation of the amniotic membrane and the pre-implanting trophoblast. Furthermore, the data suggest that Hand1 can act as a repressor by two independent mechanisms; sequestration of class A bHLH factors from E-boxes and inhibition of their transcriptional activity.

Basic Helix-Loop-Helix Proteins↗
PubMed2002

Transforming growth factor-beta 1 serum levels in pregnancy and pre-eclampsia.

BACKGROUND: Isoforms of transforming growth factor-beta (TGF-beta1) are thought to be involved in the pathogenesis of pre-eclampsia. Data with respect to TGF-beta1 are controversial. We examined the correlation between TGF-beta1 serum levels and the occurrence and severity of pre-eclampsia. METHODS: Transforming growth factor-beta 1 serum levels were measured using a commercially available enzyme-linked immunosorbent assay in 44 women with pre-eclampsia and 44 healthy pregnant women. Results were correlated with clinical data. RESULTS: No difference in TGF-beta1 serum levels was assessed between women with pre-eclampsia and healthy pregnant women. Transforming growth factor-beta 1 serum levels were not associated with the severity of the disease and were not correlated with clinical maternal (blood pressure, proteinuria) and fetal (5-min APGAR score, umbilical cord pH values, birth weight) parameters. CONCLUSIONS: Our data support the assumption that in contrast to other isoforms, TGF-beta1, as evidenced by serum TGF-beta1 levels, does not seem to be involved in the pathogenesis of pre-eclampsia.

Adult↗
PubMed2002

Development and clinical experience with the new evidence-based tocolytic atosiban.

The incidence of preterm birth has remained unchanged for the last few decades. This is due, in part, to the complex etiology of preterm labor, and the limited ability of tocolytic agents to prolong pregnancy as a result of limited efficacy and poor safety profiles. The recent introduction of the oxytocin antagonist, atosiban, represents a new generation of uterine-specific tocolytics, which are associated with more favorable safety profiles. This paper discusses the rationale behind the development of the oxytocin antagonists and provides a review of the phase II and III trials that have investigated atosiban. Also included is a retrospective analysis of 83 women assessed in the Vienna Medical School, providing an insight into the benefits associated with atosiban in the everyday clinical setting. The introduction of a safer tocolytic agent offers the potential to change the current approach to the management of preterm labor. This includes a prolonged period of treatment at earlier or later gestational ages and possibly an extended use to women with contraindications who would normally have been excluded from treatment, e.g. preterm premature rupture of the membranes.

Clinical Trials, Phase II as Topic↗
PubMed2002

Basic fibroblast growth factor and hypertensive disorders in pregnancy.

OBJECTIVE: We examined serum concentrations of basic fibroblast growth factor (bFGF) in women with hypertensive disorders in pregnancy and analyzed whether serum concentrations of bFGF can be used as a discriminator between mild and severe preeclampsia. METHODS: One hundred and twenty pregnant women were included in this prospective cohort study. We evaluated serum concentrations of bFGF in pregnant women with chronic hypertension (n=22), mild preeclampsia (n=40), severe preeclampsia (n=31), and healthy pregnant women (n=27). RESULTS: Median serum concentrations of bFGF in healthy pregnant women, women with chronic hypertension, and women with mild or severe preeclampsia were 0.0 (0-37.2), 0.0 (0-3.0), 1.7 (0-97.2), and 0.0 (0-52.0), respectively. Comparison of the median values of serum bFGF concentrations showed a significant difference between healthy pregnant women and women with mild preeclampsia (P=0.02). In a logistic regression model, we found a significant influence of bFGF serum concentrations on the diagnosis of mild preeclampsia (P=0.01), but not on the diagnosis of chronic hypertension (P=0.19) or severe preeclampsia (P=0.41). CONCLUSIONS: Elevated serum concentrations of bFGF are associated with mild preeclampsia, but are not discriminatory for the distinction between mild and severe preeclampsia.

Analysis of Variance↗
PubMed2002

[Elective caesarean section].

As a part of the ongoing debate surrounding the steady increase in the rate of caesarean sections in general, the issue of elective caesarean section - following a complication-free pregnancy and in the absence of clear medical evidence actively suggesting a caesarean section - has likewise been addressed in greater depth. The progressive decline in mortality attending a well-planned caesarean section along with the reduction in morbidity brought about by improvements in caesarean section techniques have served to direct the attention towards the less apparent maternal and fetal risks of vaginal delivery. At the same time, the growing importance attached to the patient's input has made a clear definition of the concept of 'indication' more difficult. However, the distinction between medical indications and the freedom of choice of the patient is, in the predominant number of cases, an artificial one - in the ideal scenario, obstetrician and patient arrive at a joint decision after carefully considering the advantages and disadvantages of all relevant alternatives. Hence the term 'caesarean section on demand' needs to be recognized as prejudicial and needs to be replaced with the more accurate 'elective caesarean section'. Not only is ethical dilemma avoided in the process, but medical insurance agencies are left with no reasonable grounds to refuse support to such a procedure.

Austria↗
PubMed2002

Traditional care of the perineum during birth. A prospective, randomized, multicenter study of 1,076 women.

OBJECTIVE: To investigate the influence of the traditional hands-on versus the innovative hands-poised method on the risk of perineal trauma during vaginal delivery and on neonatal outcomes. STUDY DESIGN: In a prospective, randomized, multicenter study, 1,161 of 1,505 women giving birth at the Departments of Obstetrics and Gynecology of the University Hospital of Vienna and Semmelweis Women's Hospital, Vienna, between February and September 1999, were randomized into the trial. In the hands-on method, the left hand of the midwife puts pressure on the infant's head, and the right hand is placed against the perineum. In the hands-poised method, the midwife guides the parturient through the birth without touching the perineum, prepared to apply light pressure on the infant's head. RESULTS: One hundred eighty-seven of 574 women (32.5%) in the hands-on group and 180 of 502 women (35.8%) in the hands-poised group experienced perineal tears (P = .5). Sixteen women (2.7%) treated with the hands-on method developed third-degree perineal tears as compared with five women (0.9%) treated with the hands-poised method (P < .05). In the hands-on group, 103 women (17.9%) underwent episiotomy as compared with 51 cases (10.1%) in the hands-poised group (P < .01). No significant differences in neonatal outcomes were observed between the two groups. CONCLUSION: Our data suggest that a policy of hands-poised care is more suitable for preserving the perineum during birth and is a safe and effective birthing alternative for women.

Adult↗
PubMedDate not supplied

Production of oxytocin receptor and cytokines in primary uterine smooth muscle cells cultivated under inflammatory conditions.

OBJECTIVE: We studied the production of the oxytocin receptor and interleukins in human uterine smooth muscle cells cultured in vitro in the presence of cytokines that were shown to be elevated in gestational diseases such as intrauterine infections and chorioamnionitis. METHODS: Human uterine smooth muscle cells were cultured in the absence or presence of interleukin-1beta (IL-1beta), interleukin-6 (IL-6), tumor necrosis factor alpha (TNFalpha), or lipopolysaccharide (LPS). Additionally, cells were cultivated under hypoxic conditions (3.5% oxygen). After 6, 12, 24, and 48 hours of incubation, oxytocin receptor mRNA was measured from total RNA using quantitative, competitive reverse transcriptase-polymerase chain reaction. Secreted cytokines (IL-1beta, IL-6, or IL-8) were quantitated from supernatants after 6, 12, 24, and 48 hours of stimulation by commercially available enzyme-linked immunosorbent assay. RESULTS: In nonstimulated cultures basal secretion of IL-1beta, IL-6, and IL-8 was detectable. Supplementation of IL-1beta induced a statistically significant decrease in oxytocin receptor mRNA abundance, whereas IL-6, TNFalpha, LPS, or hypoxia did not significantly affect oxytocin receptor gene expression. The cytokines IL-1 and TNFalpha induced IL-6 and IL-8 release, whereas secretion of the two interleukins was not altered in the presence of LPS or hypoxia. Expression of IL-1beta was not significantly induced under inflammatory or hypoxic culture conditions. CONCLUSION: The constitutive and cytokine-inducible expression of interleukins from uterine smooth muscle cells suggests that the myometrium may contribute to the overall production of inflammatory mediators in the uterus that are thought to govern term- or infection-induced preterm labor. Down-regulation of the oxytocin receptor under IL-1beta in myometrial cells may indicate that initiation and maintenance of labor could be partially limited under severe inflammatory conditions such as chorioamnionitis.

Cells, Cultured↗