Herbal extracts modulate the amplitude and frequency of slow waves in circular smooth muscle of mouse small intestine

Background: Herbal preparations like STW 5 (Iberogast(R)) are widely used drugs in the treatment of dyspepsia and motility-related disorders of the gastrointestinal tract. STW 5 is a phytotherapeutic agent consisting of a fixed mixture of 9 individual plant extracts. The electrophysiological mechanisms of action of STW 5 remain obscure. Aim: The aim of the present study was to investigate whether herbal extracts influence electrophysiological parameters of the small intestine. For this purpose, the resting membrane potential (RMP) and the slow wave rhythmicity of smooth muscle cells of mouse small intestine were observed. Methods: Intracellular recordings of smooth muscle cells of the circular muscle layer of mouse small intestine were performed using standard microelectrode techniques. After dissection of the mucosa, the small intestine was placed in an organ bath and a microelectrode was applied on a circular smooth muscle cell. The RMP and the amplitude of slow waves were measured in millivolts. Results: The RMP of smooth muscle cells was - 59 +/- 1.3 mV. This RMP was significantly depolarized by STW 5 ( 9.6 +/- 1.6 mV); the depolarizing effects can be mainly attributed to the constituents of matricariae flos, angelicae radix and chelidonii herba. The basal frequency of small intestinal slow waves was 39.5 +/- 1.4 min(-1) and the amplitude was 23.1 +/- 0.9 mV. STW 5 significantly reduced the amplitude and frequency of the slow waves ( 11.7 +/- 0.8 mV; 33.5 +/- 3.4 min(-1)). This effect on slow waves represents the sum of the effects of the 9 phytoextracts. Whereas angelicae radix and matricariae flos completely blocked slow wave activity, Iberis amara increased the frequency and amplitude, chelidonii herba reduced the frequency and amplitude of the slow waves, mentae piperitae folium reduced the frequency and left amplitude unchanged and liquiritae radix, carvi fructus and melissae folium had no effects. Conclusion: Herbal extracts cause changes in smooth muscle RMP and slow wave rhythmicity, up to reversible abolition, by blockade of large conductance Ca2+ channels and other not yet identified mechanisms. In herbal preparations like STW 5 these effects add up to a total effect and this study indicates that herbal preparations which are widely used in dyspepsia and motility-related disorders have characteristic, reproducible, reversible effects on small intestinal electrophysiology. Copyright (C) 2005 S. Karger AG, Basel

Septoria-like pathogens causing leaf and fruit spot of pistachio

Several species of Septoria are associated with leaf and fruit spot of pistachio (Pistacia vera), though their identity has always been confused, making identification problematic. The present study elucidates the taxonomy of the Septoria spp. associated with pistachio, and distinguishes four species associated with this host genus. Partial nucleotide sequence data for five gene loci, ITS, LSU, EF-1a, RPB2 and Btub were generated for a subset of isolates. Cylindroseptoria pistaciae, which is associated with leaf spots of Pistacia lentiscus in Spain, is characterised by pycnidial conidiomata that give rise to cylindrical, aseptate conidia. Two species of Septoria s. str. are also recognised on pistachio, S. pistaciarum, and S. pistaciae. The latter is part of the S. protearum species complex, and appears to be a wide host range pathogen occurring on hosts in several different plant families. Septoria pistacina, a major pathogen of pistachio in Turkey, is shown to belong to Pseudocercospora, and not Septoria as earlier suspected. Other than for its pycnidial conidiomata, it is a typical species of Pseudocercospora based on its smooth, pigmented conidiogenous cells and septate conidia. This phenomenon has also been observed in Pallidocercospora, and seriously questions the value of conidiomatal structure at generic level, which has traditionally been used to separate hyphomycetous from coelomycetous ascomycetes. Other than DNA barcodes to facilitate the molecular identification of these taxa occurring on pistachio, a key is also provided to distinguish species based on morphology

Are Downhill Varices an Overlooked Entity of Upper Gastrointestinal Bleedings?

Aim. Downhill varices are not so safe as thought and can lead to life-threating or mortal bleeding complication, even if rare. In order to draw attention to this topic, we analysed 129 patients. Materials and Methods. We evaluated the electronic endoscopy data records of all patients undergoing upper gastrointestinal endoscopy over a nine-year period from January 2004 till December 2012, within a retrospective approach. The primary endpoints, incidence, causes, kind of resulting upper gastrointestinal bleeding, and the severity of the bleeding were evaluated. Secondary endpoints were the evaluation of the size of downhill varices and a comparison of the risk of bleeding between downhill varices and uphill varices. Results. Downhill varices were identified, described, and/or documented in 129 patients of 25,680 upper gastrointestinal endoscopies. 26 patients had central venous catheter or port implantation, 22 patients had a history of an implantation of a cardiac pacemaker, 7 patients had severe pulmonary artery embolism, and 4 patients had severe chronic obstructive pulmonary disease. Two patients had mediastinal tumors, and one patient had a large retrosternal goiter as a possible cause of the vena cava syndrome. Altogether, 62 patients were related to a vena cava superior syndrome; 67 were not. Conclusions. Downhill varices can be seen with an incidence of 0.5%. Therapeutic means are the banding therapy as a safe and effective option. Severe bleedings associated with downhill varices can be mortal. Severe forms of downhill varices should be examined in relation to the origin in order to start a specific therapy

Characterization of Prejunctional and Postjunctional Muscarinic Receptors of the Ascending Reflex Contraction in Rat Ileum 1

ABSTRACT The ascending reflex contraction of the small intestine involves predominantly cholinergic neurotransmission. The orally projecting neural excitatory pathway of the myenteric reflex was studied in an in vitro model of rat ileal segments. The contractile response elicited by aboral field stimulation was significantly inhibited by a range of muscarinic receptor antagonists. Methoctramine and tripitramine (both M 2 selective, pIC 50 ϭ 9.3 and 8.8, respectively), darifenacin and hexahydrosiladifenidol (both M 3 selective, pIC 50 ϭ 7.3 and 7.7, respectively), and pirenzepine (M 1 selective, pIC 50 ϭ 7.0). In radioligand binding experiments on synaptosomal and smooth muscle plasma membrane fractions, we examined whether prejunctional or postjunctional muscarinic receptors exist that could potentially contribute to the reflex contraction. In the synaptosomal fraction, the muscarinic ligand In the smooth muscle plasma membrane fraction, the K d value was 0.29 Ϯ 0.05 nM and the B max value was 770 Ϯ 29 fmol/mg. The competition studies revealed a similar ratio of potency of the respective antagonists. These data suggest that muscarinic M 2 receptors, located at prejunctional and postjunctional sites, are predominantly involved in the ascending reflex contraction. Two polarized reflexes are the principal effectors of segmental and propulsive motility of the gut: the ascending excitatory and the descending inhibitory reflex Thus, it is of physiological and clinical interest to elucidate the nature of the muscarinic receptor subtypes controlling circular muscle activity and propagating neural transmission in the myenteric plexus. Receptor-binding studies in guinea pig ileum longitudinal muscle preparations demonstrated that the majority of ileal muscarinic receptors are of the M 2 subtype (ϳ80%), whereas a minority are of the M 3 subtype (ϳ20%) with no measurable quantities of M 1 or M 4 receptor