Fat Embolism Does Not Alter Cardiac Structure or Induce Pathological Changes in a Rat Model.

Introduction: Fat embolism (FE) encompasses conditions in which fatty substance becomes embedded in a tissue/organ. Fat emboli most commonly affect the lungs in a trauma setting. This can lead to both significant pathology locally and systemically including changes in structure, inflammatory response, activation of the renin-angiotensin system, and subsequent hypoxia.

Renin-Angiotensin Blockade Reduces Readmission for Acute Chest Syndrome in Sickle Cell Disease.

Rationale Acute chest syndrome (ACS) is a life-threatening complication of sickle cell disease (SCD). Current treatment is supportive-supplemental oxygen, transfusions, and antibiotics. Prevention of ACS may reduce morbidity and mortality in patients with SCD.

Evidence for angiotensin mediation of the late histopathological effects of pulmonary fat embolism: Protection by losartan in a rat model.

Purpose: In a model of fat embolism using triolein-treated rats, we have reported that the acute pulmonary histopathological changes at 48 hrs were ameliorated by the angiotensin AT1 receptor blocker losartan, the angiotensin converting enzyme inhibitor captopril, and the direct renin inhibitor aliskiren. Although much of the pathology had declined by 3 weeks, the changes persisted at 6 weeks. The purpose of the study was to extends the time course investigation to 10 weeks and to examines whether the fat embolism effects continue to be blocked by losartan when given at a late time period.

The renin inhibitor aliskiren protects rat lungs from the histopathologic effects of fat embolism.

Background: Fat embolism (FE) and the consequent FE syndrome occurring after trauma or surgery can lead to serious pulmonary injury, including ARDS and death. Current treatment of FE syndrome is limited to supportive therapy. We have shown in a rat model that the renin angiotensin system plays a significant role in the pathophysiology of FE because drugs interfering with the renin angiotensin system, captopril and losartan reduce the histopathologic pulmonary damage.

Fat embolism sensitizes rats to a "second hit" with lipopolysaccharide: An animal model of pulmonary fibrosis.

Background: Pulmonary fat embolism (FE) in patients after major bone fracture and other trauma may lead to acute respiratory distress, but few clinical evidence of lung injury remains, and there is a dearth of histopathologic information after the initial recovery. We recently reported histologic changes in the lungs of a patient who died after cesarian delivery, which were similar to a rat model of FE. In this model, we found that despite an apparent full recovery, modest fibrotic damage persisted up to 6 weeks.

Persistent and progressive pulmonary fibrotic changes in a model of fat embolism.

Background: Fat embolism (FE) after trauma and some orthopedic procedures is known to cause acute lung injury, including acute respiratory distress syndrome. However, its potential long-term effects on the lung are unknown. A previous study using a rat model of FE found significant histopathologic changes in the lungs after intravenous injection of triolein for up to 11 days.

Mitigating effects of captopril and losartan on lung histopathology in a rat model of fat embolism.

Background: Fat embolization (FE) is an often overlooked and poorly understood complication of skeletal trauma and some orthopedic procedures. Fat embolism can lead to major pulmonary damage associated with fat embolism syndrome (FES).

Methods: A model of FE in unanesthetized rats, using intravenous injection of the neutral fat triolein, was used to study the potential therapeutic effect on lung histopathology of altering the production of, or response to, endogenous angiotensin (Ang) II.

Fat embolism: evolution of histopathological changes in the rat lung.

The pathophysiology of Fat Embolism Syndrome (FES) is poorly understood and subject to some controversy. Evaluation of the evolution of histological changes in the lungs of patients with FES is impractical. The current theories of FES were established through acute clinical observations and acute animal experiments, but sequential changes in the histology of lungs over a prolonged period have not been made.

Estrogens act in rat hippocampus and frontal cortex to produce rapid, receptor-mediated decreases in serotonin 5-HT(1A) receptor function.

Previously our laboratory has shown that 17beta-estradiol in vivo rapidly decreases R(+)-8-OH-DPAT-stimulated [(35)S]GTPgammaS binding (a measure of the initial biochemical event in the intracellular signaling pathway associated with 5-HT(1A) receptors) in the hippocampus, frontal cortex and amygdala. Studies were designed to determine if 17beta-estradiol also acts in vitro on estrogen receptors in the hippocampus and frontal cortex to decrease 5-HT(1A) receptor function. Hippocampus and frontal cortex were dissected from ovariectomized rats and incubated for up to 3 h with various estrogens and antiestrogens; membrane homogenates were prepared for R(+)-8-OH-DPAT-stimulated [(35)S]GTPgammaS binding assays.

The human placental renin-angiotensin system.

The human placenta and related tissues are considered to be examples of the recently accepted local renin-angiotensin systems (RAS). The brain is another example of a system that is thought to be regulated independently of the kidney and the role of angiotensin within the CNS as a neural mediator has drawn considerable attention. It has been known for a long time that many of the neuroendocrine mediators and receptors are expressed in the placenta and it has been suggested that there are many parallels between the classical neuroendocrine system and the placental one.

Beta-adrenergic regulation of renin expression in differentiated U-937 monocytic cells.

Previous studies from our laboratories demonstrated that human decidual macrophages and peripheral mononuclear cells express renin. In the present study, we found that U-937 monocytes, induced to differentiate into macrophage-like cells by treatment with phorbol dibutyrate (PDBU), express renin mRNA and release renin (95%, of which is in the form of prorenin). Treatment of these PDBU-exposed cells with dibutyryl-cAMP (1 mM) caused a 20-fold increase in renin mRNA and a 10-fold increase in prorenin release.

Beta-adrenoceptor activation-induced placental prorenin secretion is mediated by increased renin messenger RNA and protein synthesis.

Activation of beta-adrenoceptors has been shown to promote renin secretion in both human kidney and placenta. In kidney, the enhanced secretion is immediately observed, and mobilization of renin in the storage granules accounts for such a rapid response. In contrast, the enhanced secretion in placenta is delayed for 6-12 hr after receptor activation and consists almost entirely of the renin precursor prorenin.

Interferon-gamma inhibits the synthesis and release of renin from human decidual cells.

Experiments were performed to examine the effect of interferon-gamma (IFN gamma) on the expression of renin by human uterine decidual cells and decidual macrophages. Exposure of a mixed population of decidual cells consisting of 80% decidualized stromal cells and 20% macrophages to IFN gamma for 4 days caused a dose-dependent inhibition of renin release beginning 2 days after exposure. Renin release on Day 4 was inhibited by a maximum of 83.

Human chorionic gonadotropin stimulates placental prorenin secretion: evidence for autocrine/paracrine regulation.

Functional regulation of the placental renin-angiotensin system remains incompletely defined. Evidence indicates that synthesis and secretion of prorenin in the placenta and gestational sac decrease with advancing gestational age. Possible explanations for this developmental effect include the regulatory influences by locally released hormones, such as CG.

Stimulation of placental prorenin secretion by selective inhibition of cyclic nucleotide phosphodiesterases.

Prorenin secretion by human villous placenta is known to be stimulated by activation of adenylate cyclase and enhanced cyclic AMP (cAMP) generation. Placental tissue contains predominantly type III (cGMP-inhibited) and type IV (cAMP-specific) phosphodiesterases (PDEs), which inactivate cAMP. To evaluate the role of PDE subtypes in the regulation of prorenin secretion by human placenta, explants were cultured in the presence of isobutylmethylxanthine (IBMX), a non-selective PDE inhibitor, and selective inhibitors for various PDE subtypes.

Human uterine decidual macrophages express renin.

Human uterine decidual tissue contains many cell types, including stromal cells, fibroblasts, and macrophages. Earlier studies have shown that decidualized uterine stromal cells express renin, primarily in the form of prorenin. However, the possibility that decidual macrophages, which comprise about 30% of the cells in term decidua, also express renin has not been investigated.

First-trimester villous placenta has high prorenin and active renin concentrations.

Objective: Term villous placental concentrations of prorenin are known to be very low, whereas those of decidua and fetal membranes are high. It has been demonstrated that prorenin synthesis is modulated by hormones in other reproductive tissues, thus suggesting a means for paracrine regulation in the placenta. This study was performed to test the hypothesis that placental tissue prorenin concentrations may be influenced by gestational age and are temporally related to alterations in the hormonal milieu.

Tumor necrosis factor-alpha and interleukin-1 beta inhibit the synthesis and release of renin from human decidual cells.

Cytokines modulate hormone expression in many cell types, including the expression of renin in juxtaglomerular cells. However, the effect of cytokines on the expression of renin from extrarenal cells is unknown. In this paper, we have examined whether tumor necrosis factor-alpha (TNF alpha) and interleukin-1 beta (IL-1 beta) modulate the release of renin from human decidual cells.

Regulation of utero-placental prorenin.

Prorenin (Pro) is synthesized in a number of human utero-placental tissues, including chorion, decidua, villous placenta and probably mesenchymal cells. The release of Pro from these extra-renal tissues follows new protein synthesis and appears to utilize the constitutive secretory pathway. Unlike processing in the kidney, very little of the Pro is subsequently cleaved to the smaller product (active renin).

cAPK mediates placental renin secretion stimulated by beta-adrenoceptor activation.

Previous studies have indicated that activation of placental beta-adrenoceptors stimulates renin secretion, whereas basal secretion is extremely low. This response is potentiated by inhibition of types III and IV phosphodiesterases, implicating a role for adenosine 3',5'-cyclic monophosphate (cAMP). Described are experiments aimed at defining the regulatory influence of cAMP and cAMP-dependent protein kinase (cAPK) isotypes in renin secretion.

Endothelin-1 modulates renin and prolactin release from human decidua by different mechanisms.

Endothelin (ET)-1 stimulates the synthesis and release of renin and inhibits the expression of prolactin (PRL) from term human decidual cells. To examine the mechanisms by which ET-1 exerts its differential effects on renin and PRL expression, we have studied total renin and PRL release from term human decidual cells in response to pharmacological agents that affect calcium- and protein kinase C-dependent mechanisms. Calcium ionophore A-23187 stimulated basal renin release and potentiated ET-1-stimulated renin release but had no effect on basal or ET-inhibited PRL release.

Prorenin secretion from villous placenta: regulation by cyclic AMP and angiotensin.

Renin synthesis and secretion from human chorion and decidua have previously been shown to be stimulated by agents which increase cellular cyclic adenosine monophosphate (cAMP). We have now used organ culture of villous placenta, incubated for periods up to 72 h, to investigate the cellular regulation of renin in this tissue. The placental tissues release renin (92-96% in the form of prorenin) and human chorionic gonadotrophin (hCG), but not prolactin.

Regulation of tyrosine hydroxylase gene expression in depolarized non-transformed bovine adrenal medullary cells: second messenger systems and promoter mechanisms.

Activation of the tyrosine hydroxylase (TH) gene in the adrenal medulla during stress is mediated by trans-synaptic mechanisms and may involve cholinergic receptors. Stimulation of nicotinic receptors in adrenal medullary cells induces cell depolarization, influx of Ca2+ ions and increases levels of cAMP. We have shown that both cAMP and membrane depolarization produce an increase in the expression of the TH gene in cultured bovine adrenal medullary cells (BAMC).

Lipopolysaccharides inhibit prolactin and renin release from human decidual cells.

Human decidual tissue consists of a heterogeneous population of cells, including stromal cells, lymphocytes, and macrophages. Lipopolysaccharides (LPS), which bind to specific cell surface receptors on macrophages, have been shown to increase prostaglandin production by the decidua and amnion. To determine whether LPS may also affect decidual hormone production, we have examined the effects of LPS on the synthesis and release of prolactin and renin.