Modulation of myocardial contractility by lysophosphatidic acid (LPA)

Lysophosphatidic acid (LPA) is a phospholipid messenger, which is released from activated platelets and leukocytes. This study examined the effects of LPA on myocardial contractility and characterized the signal transduction pathway involved in these effects. Functional effects of LPA were determined in isolated, electrically driven human myocardial preparations and rat cardiac myocytes. In human atrial and ventricular myocardial preparations, LPA (100 micromol/l) decreased isoprenaline (0.03 micromol/l) enhanced force of contraction by 17 +/- 2% and 28 +/- 3%, respectively. The effect of LPA was attenuated by suramin (1 mmol/l). In isolated rat cardiomyocytes, LPA (1-100 micromol/l) concentration dependently abolished isoprenaline (0.03 micromol/l) induced increase in cell shortening. This antiadrenergic effect was blunted after pretreatment with pertussis toxin (5 microg/ml, 12 h). Forskolin (10 micromol/l) stimulated adenylyl cyclase activity was inhibited by LPA in human myocardial membranes. PCR analysis of human atrial and ventricular cDNAs revealed the expression of two cognate LPA receptors: EDG-2 and EDG-7. Our results suggest that LPA exerts antiadrenergic effects on force of contraction in human and rodent myocardium via a Galpha(i/o) protein-mediated mechanism, most probably by LPA binding to the mammalian LPA receptors EDG-2 and/or EDG-7. This newly discovered action of LPA might be of pathophysiological importance in conditions like myocardial ischemia or inflammatory disorders when LPA release is enhanced.     

Pharmacokinetic and pharmacodynamic drug interactions with Kava (Piper methysticum Forst. f.)

Kava kava, a beverage or extract prepared from the rhizome of the kava plant (Piper methysticum Forst. f.), was used for many centuries as a traditional beverage in the Pacific Islands. During the past few decades, kava has also gained popularity in Western countries as well, due to its anxiolytic and sedative properties. However, in recent years, kava has been implicated in several liver failure cases which led to its ban in many countries and this has prompted wide discussion on its relative benefits and risks as a social beverage and a herbal remedy. Recently, it has been shown that several kavalactones, the assumed active principles of kava extracts, are potent inhibitors of several enzymes of the CYP 450 system (CYP1A2, 2C9, 2C19, 2D6, 3A4 and 4A9/11). This indicates that kava has a high potential for causing pharmacokinetic drug interactions with other herbal products or drugs, which are metabolised by the CYP 450 enzymes. In addition, several pharmacodynamic interactions have been postulated and indeed observed. Nevertheless, evidence of true pharmacokinetic and/or pharmacodynamic interactions remains unsubstantiated, and only few investigations of the potential of kava preparations to interact with specific drugs have been carried out. This review provides a critical overview of the existing data on interactions of kava with other drugs and concludes that there is an urgent need for further in vitro and in vivo investigations to fully understand clinically significant interactions with kava that have the potential to cause adverse effects or toxicity in kava users.     

New peptaibols from Mycogone cervina

From cultures of Mycogone cervina, a mycophilic fungus growing on the fruit bodies of ascomycete Paxina acetabulum, two new peptaibols (cervinin, N-Ac-Leu-Aib-Pro-Aib-Leu-Aib-Pro-Ala-Aib-Pro-Val-red-Leu (1) and the red-Leu O-acetylated derivative 2) were isolated. The structures of 1 and 2 were elucidated by spectroscopic techniques. They exhibited weak antibacterial as well as cytotoxic activities. They are the first secondary metabolites described from M. cervina.     

Silver-coated textiles reduce Staphylococcus aureus colonization in patients with atopic eczema

BACKGROUND: In atopic eczema (AE), skin colonization with Staphylococcus aureus is known to play a major triggering and possibly pathophysiological role. METHODS: In this open-labeled controlled side-to-side comparative trial, affected sites (flexures of both elbows) in 15 patients diagnosed as having generalized or localized AE were evaluated regarding S. aureus colonization and clinical severity of AE over a 2-week period. Flexures of the elbows were covered with silver-coated textiles on one arm and cotton on the other for 7 days followed by a 7-day control period. RESULTS: A highly significant decrease in S. aureus colonization could be seen on the site covered by the silver-coated textile already 2 days after initiation lasting until the end of the treatment. Seven days after cessation, S. aureus density remained significantly lower compared to baseline. In addition, significantly lower numbers of S. aureus were observed on the silver-coated textile site in comparison to cotton at the end of treatment as well as at the time point of control. Clinical improvement correlated with the reduction of S. aureus colonization. CONCLUSION: A superior improvement achieved by silver-coated compared to cotton textiles paralleled a potent anti-S.-aureus effect.     

Posttraumatic stress disorder following assault: the role of cognitive processing,trauma memory,and appraisals

Two studies of assault victims examined the roles of (a) disorganized trauma memories in the development of posttraumatic stress disorder (PTSD), (b) peritraumatic cognitive processing in the development of problematic memories and PTSD, and (c) ongoing dissociation and negative appraisals of memories in maintaining symptomatology. In the cross-sectional study (n = 81), comparisons of current, past, and no-PTSD groups suggested that peritraumatic cognitive processing is related to the development of disorganized memories and PTSD. Ongoing dissociation and negative appraisals served to maintain PTSD symptoms. The prospective study (n = 73) replicated these findings longitudinally. Cognitive and memory assessments completed within 12-weeks postassault predicted 6-month symptoms. Assault severity measures explained 22% of symptom variance; measures of cognitive processing, memory disorganization, and appraisals increased prediction accuracy to 71%.     

The serum protein alpha 2-Heremans-Schmid glycoprotein/fetuin-A is a systemically acting inhibitor of ectopic calcification

Ectopic calcification is a frequent complication of many degenerative diseases. Here we identify the serum protein alpha2-Heremans-Schmid glycoprotein (Ahsg, also known as fetuin-A) as an important inhibitor of ectopic calcification acting on the systemic level. Ahsg-deficient mice are phenotypically normal, but develop severe calcification of various organs on a mineral and vitamin D-rich diet and on a normal diet when the deficiency is combined with a DBA/2 genetic background. This phenotype is not associated with apparent changes in calcium and phosphate homeostasis, but with a decreased inhibitory activity of the Ahsg-deficient extracellular fluid on mineral formation. The same underlying principle may contribute to many calcifying disorders including calciphylaxis, a syndrome of severe systemic calcification in patients with chronic renal failure. Taken together, our data demonstrate a critical role of Ahsg as an inhibitor of unwanted mineralization and provide a novel therapeutic concept to prevent ectopic calcification accompanying various diseases.     

Mirtazapine (Remergil) for treatment resistant hyperemesis gravidarum: rescue of a twin pregnancy

Case report We present the case of a 25-year-old woman with treatment resistant hyperemesis gravidarum in the 15th week with a 13 kg loss of body weight. When the patient asked for termination of the pregnancy because of the unbearable symptoms, treatment with intravenous mirtazapine (Remergil) was started.Results Nausea and vomiting disappeared within hours, pregnancy termination was no longer desired. The patient was discharged two weeks later in good health and at 36 weeks gestation a cesarean section was performed. Post partum evaluation as well as 6-month post-partum revealed no dysmorphology or laboratory abnormalities in the children.     

Cimicifuga extract BNO 1055: reduction of hot flushes and hints on antidepressant activity

Ethanolic- and isopropanolic-aqueous extracts of Cimicifuga racemosa are used for the treatment of climacteric complaints. As hot flushes and psychic complaints seem to be special targets for Cimicifuga extracts in clinical studies, these parameters were studied in experimental animals. Hot flush equivalents were measured in castrated rats as a quick increase in peripheral temperature with the aid of a transmitter implanted subcutaneously on the ventral side. The hot flush equivalents proved to respond to estrogen and the antidopaminergic drug veralipride but they were also reduced very effectively by Cimicifuga extract BNO 1055 (which is contained in Klimadynon/Menofem). In addition, an ethanolic-aqueous extract of C. racemosa was studied in the tail suspension test (TST), a behavioural test indicative for antidepressant activity. A significant decrease of the period of immobility was observed after treatment with 30 mg/kg body weight (bw) imipramine or with 50 or 100 mg/kg bw Cimicifuga extract. These findings in pharmacological tests-a reduction of the frequency of hot flush equivalents and hints on antidepressant activity of Cimicifuga extracts-are in good agreement with the therapeutical responses in climacteric women.