Reinfektionsversuche an Lymnaea stagnalis mit Isthmiophora melis (Trematoda,Echinostomatidae) durch Miracidienexposition nach vorausgegangener Redienimplantation

Zusammenfassung Die natürliche intramolluskäre Entwicklung des Darmegels Isthmiophora melis verläuft über zwei morphologisch distinkte Redienformen: Auf zwei Generationen makropharyngeater Redien (Mutterredien) folgen nur noch Generationen mikropharyngeater Redien (Tochterredien) sowie Cercarien. Die Bildung von Mutterredien unterbleibt in Schnecken, die nur durch Implantation von Tochterredien experimentell infiziert wurden. Werden Schnecken nacheinander beiden Infektionsmodi unterworfen, der Tochterredienimplantation und der Miracidienexposition, so läßt sich aus dem Vorhandensein oder Fehlen von Mutterredien ablesen, welche der Infektionen von Erfolg war.Mittels dieser Methode wurde geprüft, ob Isthmiophora-parasitierte Lymnaea-Individuen gegen homologen Miracidienbefall resistent sind. Sie erwiesen sich als nicht resistent gegen Reinfektion, und zwar auch dann, wenn sie bereits in die Phase des Cercarienausstoßes eingetreten waren.

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Experimental re-infection of Lymnaea stagnalis with Isthmiophora melis (trematoda, echinostomatidae) by exposition to miracidia after implantation of rediae

Summary The natural intramolluscular development of the intestinal fluke Isthmiophora melis takes place in two morphologically distinct forms of rediae: Two generations of macropharyngeate rediae (mother rediae) are followed only by generations of micropharyngeate rediae (daughter rediae) and cercariae. Mother rediae are not produced in snails infected by implantation of daughter rediae only. If snails are subjected to the implantation of daughter rediae and exposed to miracidiae successsively, the presence, or absence, of mother rediae indicates which of the infections has been successful.This method of investigation was used in order to ascertain whether Lymnaea individuals parasitized by Isthmiophora are resistant against invading miracidia of homologous species. They proved not resistant against re-infection, even if they had already entered the stage of shedding cercariae.

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Ermöglicht durch Beihilfen der Deutschen Forschungsgemeinschaft.     

Evidence for a change in the expression of beta2-microglobulin-assoicated membrane structures on leukaemic human cells.

Cell-associated and serum beta2-microglobulin was estimated in seven patients with chronic lymphocytic leukaemia. The amount of cell-associated beta2-microglobulin was significantly reduced (P less than 0.01), due to a decrease in the fraction of beta2-microglobulin that passes unretarded through a concanavalin A affinity column (presumably non-HLA-associated beta2-microglobulin). Serum concentrations of beta2-microglobulin were increased, but no correlation was found between the decrease in cell-associated beta2-microglobulin and the increase in serum beta2-microglobulin. All of the beta2-microglobulin from leukaemic serum was eluted corresponding to a molecular weight of 11,800 and none of it was retarded on a concanavalin A affinity column. The decrease in cell-associated beta2-microglobulin might reflect a change in the qualitative or quantitative expression of beta2-microglobulin-associated membrane structures on the leukaemic cells, perhaps conferring resistance to the cells against hypothetical immunological host defence mechanisms.     

A New Care Model Reduces Polypharmacy and Potentially Inappropriate Medications in Long-Term Care

ObjectivesAssess the impact of a new pharmaceutical care model on (1) polypharmacy and (2) potentially inappropriate medication (PIM) use in long-term care facilities (LTCFs).DesignPragmatic quasi-experimental study with a control group. This multifaceted model enables pharmacists and nurses to increase their professional autonomy by enforcing laws designed to expand their scope of practice. It also involves a strategic reorganization of care, interdisciplinary training, and systematic medication reviews.Setting and ParticipantsTwo LTCFs exposed to the model (409 residents) were compared to 2 control LTCFs (282 residents) in Quebec, Canada. All individuals were aged 65 years or older and residing in included LTCFs.MeasuresPolypharmacy (≥10 medications) and PIM (2015 Beers criteria) were analyzed throughout 12 months between March 2017 and June 2018. Groups were compared before and after implementation using repeated measures mixed Poisson or logistic regression models, adjusting for potential confounding variables.ResultsOver 12 months, for regular medications, polypharmacy decreased from 42% to 20% (exposed group) and from 50% to 41% (control group) [difference in differences (DID): 13%, P < .001]. Mean number of PIMs also decreased from 0.79 to 0.56 (exposed group) and from 1.08 to 0.90 (control group) (DID: 0.05, P = .002).Conclusions and ImplicationsCompared with usual care, this multifaceted model reduced the probability of receiving ≥10 medications and the mean number of PIMs. Greater professional autonomy, reorganization of care, training, and medication review can optimize pharmaceutical care. As the role of pharmacists is expanding in many countries, this model shows what could be achieved with increased professional autonomy of pharmacists and nurses in LTCFs.     

Progressive atrophy of the frontal lobes in first-episode schizophrenia: interaction with clinical course and neuroleptic treatment

OBJECTIVE: This prospective study examined the interaction of clinical course of disease and brain structure with time in schizophrenic patients. METHOD: A total of 21 first-episode schizophrenic patients, 10 patients with other psychiatric disorders and a control group of 9 healthy volunteers had CT at first admission and at reinvestigation 5 years later. RESULTS: At first admission all of the patients had enlarged cortical fissures and sulci compared to controls, and the duration of untreated psychosis was significantly correlated with sulcal enlargement. At reinvestigation, frontal and central brain atrophy had progressed in schizophrenic patients. CONCLUSION: The study indicated that ongoing psychosis and lifetime dose of classical antipsychotics were the main candidates accounting for the finding of progressively disturbed brain structure during the first 5 years of schizophrenia.     

The Antiarrhythmic Drug BRL‐32872

BRL‐32872 is a new antiarrhythmic drug with balanced class‐III and class‐IV actions as categorized by the Vaughan‐Williams classification. BRL‐32872 blocks the rapid component of the cardiac delayed rectifier potassium channel IK_r (IC₅₀= 28 nM) and its molecular correlate HERG (“Human‐ether‐a‐go‐go related gene,” IC₅₀ of 19.8 nM in cell lines) at low concentrations. It also inhibits the L‐type calcium current (ICa) at higher concentrations (IC₅₀= 2.8 μM). This dual concentration‐dependent profile of action at higher concentrations may possibly prevent “torsades de pointes” ventricular arrhythmias, which is a dangerous side effect of many other class‐III antiarrhythmic drugs. With BRL‐32872, an excessive prolongation of the action potential duration and consecutive QTc prolongation is prevented by a concentration‐dependent increase of calcium channel block, resulting in the so‐called “bell‐shaped” profile of antiarrhythmic drug action. BRL‐32872 is very effective in the treatment of ventricular arrhythmias in animal models of cardiac ischemia. In the ischemic hearts of animals the drug significantly reduced early afterdepolarization and ventricular tachycardia. The antiarrhythmic effect of BRL‐32872 has not yet been demonstrated in humans.     

Alpha,beta hybrid peptides: a polypeptide helix with a central segment containing two consecutive beta-amino acid residues

Conformational studies on the synthetic 11-aa peptide t-butoxycarbonyl (Boc)-Val-Ala-Phe-alpha-aminoisobutyric acid (Aib)-(R)-beta3-homovaline (betaVal)-(S)-beta3-homophenylalanine (betaPhe)-Aib-Val-Ala-Phe-Aib-methyl ester (OMe) (peptide 1; betaVal and betaPhe are beta amino acids generated by homologation of the corresponding l-residues) establish that insertion of two consecutive beta residues into a polypeptide helix can be accomplished without significant structural distortion. Crystal-structure analysis reveals a continuous helical conformation encompassing the segment of residues 2-10 of peptide 1. At the site of insertion of the betabeta segment, helical hydrogen-bonded rings are expanded. A C15 hydrogen bond for the alphabetabeta segment and two C14 hydrogen bonds for the alphaalphabeta or betaalphaalpha segments have been characterized. The following conformational angles were determined from the crystal structure for the beta residues: betaVal-5 (= -126 degrees, = 76 degrees, and psi = -124) and betaPhe-6 (=-88 degrees, = 80 degrees, and psi =-118). The N terminus of the peptide is partially unfolded in crystals. The 500-MHz 1H-NMR studies establish a continuous helix over the entire length of the peptide in CDCl3 solution, as evidenced by diagnostic nuclear Overhauser effects. The presence of seven intramolecular hydrogen bonds is also established by using solvent dependence of NH chemical shifts.