Magnetic Marker Monitoring offers an alternative to investigate the behavior of solid dosage forms in the organs of the gastrointestinal tract without the need to apply radiation. For Magnetic Marker ...Monitoring, the dosage form is marked as a permanent magnetic dipole by the incorporation of small amounts of ferromagnetic material, as for example the colorant black iron oxide, and subsequent magnetization. Thereby, the dosage form is labeled as the source of a well defined magnetic field, which can be measured using a measurement technique that is established for biomagnetic investigations. Using the established concepts for magnetic source localization, the three dimensional localization and orientation as well as the strength of the magnetic source can be reconstructed from these magnetic measurement data as a function of time. Furthermore, it is possible to gain quantitative information on the disintegration of dosage forms in vivo. Examples are given for results obtained concerning the esophageal transit, the gastric and the intestinal behavior of capsules and tablets.
Bile acid diarrhea is one of the most frequently undiagnosed causes of chronic diarrhea. A variety of different pathophysiologic causes can underlie chronic diarrhea. Even after exclusion of the more ...frequent causes, up to 5 % of the population remains affected by unexplained chronic diarrhea. In up to 50 % within this cohort, bile acid diarrhea is the underlying cause.The various pathophysiologies leading to bile acid diarrhea are well characterized. In this way, bile acid diarrhea can be divided into primary, secondary and tertiary subtypes. Common to all causes is the increased amount of bile acids in the colon and in the faeces and the resulting secretory-osmotic diarrhea, in more severe forms in combination with steatorrhea. The diagnosis of bile acid diarrhea follows a clear algorithm which, in addition to the search for the cause and possibly a therapeutic trial, recognizes the 75SeHCAT test as the reference method for the detection of an increased loss of bile acids. In view of the chronic nature of the symptoms and the need for permanent, lifelong therapy, the use of a one-time, reliable diagnostic test is justified, though the test is currently only available at a few centers. In addition to the treatment of identifiable underlying diseases, the current treatment includes the use of drugs that bind bile acids, with additional nutritional recommendations and vitamin substitutions.The present review article summarizes the pathophysiology and importance of bile acid diarrhea and discusses the current approach towards diagnosis and treatment.
Is desacyl ghrelin a modulator of food intake? Inhoff, Tobias; Wiedenmann, Bertram; Klapp, Burghard F. ...
Peptides (New York, N.Y. : 1980),
05/2009, Letnik:
30, Številka:
5
Journal Article
Recenzirano
Desacyl ghrelin is produced in the gastric mucosa and plasma by deacylation of ghrelin. It occurs in considerably larger amounts than ghrelin in various regions in the organisms of rats and mice. It ...exerts biological activities
in vitro as different as stimulating adipogenesis or inhibiting glucose output in hepatocytes. In fasted rats, desacyl ghrelin levels decreased under catabolic metabolic conditions and in mice, high desacyl ghrelin concentrations went along with decreased food intake. These observations suggest an influence of the peptide on food intake and energy homeostasis. Behavioral studies led to controversial results, but several suggest an anorexigenic effect. Studies on desacyl ghrelin-induced modulation of food intake indicate the involvement of central nervous pathways, since it is said to cross the blood–brain barrier and to induce increased neuronal activity hypothalamic nuclei. It is likely to be involved in the regulation of the synthesis of anorexigenic hypothalamic mediators. Quite possibly, there might be means of interaction between desacyl ghrelin and its supposable precursor ghrelin.
The prediction of the
in vivo drug release characteristics of modified release oral dosage forms by
in vitro dissolution tests is a prerequisite for successful product development. A novel ...dissolution test apparatus that mimics the physical conditions experienced by an oral formulation during gastrointestinal transit was developed. This included the simulation of pressure forces exerted by gut wall motility, shear forces generated during propagation, and loss of water contact when the dosage form is located in an intestinal air pocket. The new apparatus was evaluated using a diclofenac extended release (ER) tablet. The
in vitro dissolution profiles were compared between the novel test apparatus and a conventional dissolution apparatus (USP II). These data were compared with the profiles of plasma concentration versus time that were obtained after the administration of an ER tablet to 24 healthy volunteers under fasting conditions. Multiple peaks were observed in individual plasma concentration–time profiles after the intake of the reference ER tablet. Standard dissolution testing showed typical characteristics of an almost continuous release for this formulation; however, dissolution testing with the novel apparatus suggested that the diclofenac release from the ER tablets would be extremely variable and dependent on the applied stress. The data suggest that the observed multiple peaks of plasma concentration after dosing of the ER diclofenac tablets are most probably caused by sensitivity to physical stress events during gastrointestinal transit.
Background
Irritable bowel syndrome (IBS) is associated with reduced quality of life and high healthcare costs. This study aimed to assess the prevalence and risk factors for IBS in a general adult ...population.
Methods
The Study of Health in Pomerania (SHIP) is a population‐based cohort study in northeastern Germany. SHIP‐Trend‐0 participants enrolled from 2008 to 2012 were grouped according to Rome III criteria (main criteria: abdominal discomfort or crampy or bloating pain for at least six months plus 2/3 additional criteria). Factors associated with IBS were assessed using survey‐weighted backward stepwise logistic regression.
Key Results
The final data set included 4194 records. IBS prevalence was 3.5% (3.0%‐4.2%). Unemployment (OR: 2.02, 1.26‐3.21), headaches (OR: 2.37, 1.59‐3.52), mental quality of life (OR: 0.95 per unit increase, 0.93‐0.97), and interactions between gender and physical quality of life (P = 0.004) and gender and alexithymia (P = 0.002) predicted IBS probability. The model resulted in a good discrimination (area under the curve = 75.4%) and model fit (F = 0.72, P = 0.69). History of depression (OR: 2.77, 1.94‐3.95), back pain (OR: 2.38, 1.69‐3.35), early trauma (OR: 1.03, 1.02‐1.04), and duration of inpatient treatment within the last twelve months (OR: 1.02, 1.01‐1.04) lost their significance in multivariable analysis.
Conclusions & Inferences
IBS prevalence was relatively low compared to other studies. Factors predicting IBS were of biological, psychological, and social nature. The association between IBS and pain in different areas of the body indicates a potential underlying complex somatic symptom disorder.
Prevalence of irritable bowel syndrome (IBS) is reported to be heterogeneous and depends on the investigated population and the applied diagnostic criteria. This study aimed to assess prevalence and risk factors for IBS in one of the largest representative population‐based studies assessing IBS in Germany. IBS prevalence was comparatively low; predicting IBS, key factors were unemployment, gender, headaches, physical and mental quality of life.
Nahrungsmittelallergien und andere -unverträglichkeiten Kleine-Tebbe, Jörg; Waßmann-Otto, Anja; Mönnikes, Hubert
Bundesgesundheitsblatt, Gesundheitsforschung, Gesundheitsschutz,
06/2016, Letnik:
59, Številka:
6
Journal Article
Recenzirano
Zusammenfassung
Eine immunologische Unverträglichkeit gegen Nahrungsmittel (NM) ist als Nahrungsmittelallergie (NMA) definiert. Hierbei handelt es sich meist um durch Immunglobuline der Klasse E ...(IgE) bedingte Soforttypreaktionen (Typ-I-Allergie) mit möglicher Beteiligung von Schleimhäuten, Haut, Atemwegen, Verdauungstrakt und Kreislauf. Primäre NMA beruhen auf (vorhergegangener) IgE-Sensibilisierung gegen tierische (z. B. in Kuhmilch, Hühnerei) oder pflanzliche Proteine (z. B. in Erdnuss, Haselnuss oder Weizen). Bei sekundären NMA reagiert IgE gegen Pollenproteine (z. B. Birke) auf strukturell ähnliche NM-Proteine (mit Kreuzallergie auf Kern- und Steinobst). Nichtimmunologische NM-Unverträglichkeiten sind meist Kohlenhydratmalassimilationen (z. B. Laktoseintoleranz, Fruktosemalabsorption) und ganz selten Pseudoallergien (z. B. gegen Aroma-, Farb-, Konservierungsstoffe), die bevorzugt bei Patienten mit chronischer Urtikaria auftreten. Häufige Verdauungsprobleme beruhen meist auf funktionellen Beschwerden (z. B. Reizdarmsyndrom), selten auf entzündlichen Darmerkrankungen (z. B. Zöliakie). Histaminintoleranz, Glutenhypersensitivität und angebliche NM-Typ-III-Allergien sind umstrittene Diagnosen. Die dargestellten Krankheitsbilder und -modelle besitzen für die Betroffenen, das Gesundheitssystem und die Gesellschaft unterschiedlichste Bedeutung.
Brain corticotropin-releasing factor (CRF) is involved in stress-induced accelerated colonic transit. Brain sites of action of CRF to stimulate colonic transit were investigated in conscious fed ...rats.
Bilateral guide cannulae were chronically implanted into the paraventricular nucleus of the hypothalamus (PVN) or central amygdala for peptide microinjection and a catheter into the proximal colon to measure colonic transit.
CRF (0.6 nmol/rat) injected into the PVN reduced colonic transit time by 84% and stimulated fecal pellet output 20-fold, whereas CRF injected into sites outside of the PVN or the central amygdala had no effect. CRF stimulatory action was prevented by chlorisondamine, and atropine methyl nitrate but not by bretylium. The stress of avoiding water by standing on a small cube reduced colonic transit time by 75% and increased fecal output by 7-fold. Bilateral microinjection of CRF antagonist, alpha-helical-CRF, into the PVN abolished the colonic response to stress. The CRF antagonist had no effect on basal colonic transit time in nonstressed rats.
Psychological stress-induced stimulation of colonic motor function in fed rats involves CRF pathways in the PVN.
Diarrhea predominant irritable bowel syndrome (IBS-D) is a complex disorder related to dysfunctions in the serotonergic system. As cis-regulatory variants can play a role in the etiology of complex ...conditions, we investigated the untranslated regions (UTRs) of the serotonin receptor type 3 subunit genes HTR3A and HTR3E. Mutation analysis was carried out in a pilot sample of 200 IBS patients and 100 healthy controls from the UK. The novel HTR3E 3′-UTR variant c.*76G>A (rs62625044) was associated with female IBS-D (P = 0.033, OR = 8.53). This association was confirmed in a replication study, including 119 IBS-D patients and 195 controls from Germany (P = 0.0046, OR = 4.92). Pooled analysis resulted in a highly significant association of c.*76G>A with female IBS-D (P = 0.0002, OR = 5.39). In a reporter assay, c.*76G>A affected binding of miR-510 to the HTR3E 3′-UTR and caused elevated luciferase expression. HTR3E and miR-510 co-localize in enterocytes of the gut epithelium as shown by in situ hybridization and RT–PCR. This is the first example indicating micro RNA-related expression regulation of a serotonin receptor gene with a cis-regulatory variant affecting this regulation and appearing to be associated with female IBS-D.
It is well established that autonomic control of digestive function is modulated by central autonomic neurotransmission. In this context it has been shown that digestive function can be modulated by ...exogenous neuropeptides microinjected into specific brain sides. Furthermore, there is considerable evidence suggesting that neurons projecting from the arcuate nucleus (ARC) to the PVN may be the source of endogenous neuropeptide release in the PVN. Neuronal projections from the ARC have been proposed to target corticotropin-releasing factor (CRF)-positive neurons in the PVN. Exogenous CRF in the PVN has been shown to modulate digestive function like gastric acid secretion and GI motility. Recently we have demonstrated that activation of ARC neurons inhibits gastric acid secretion via central CRF receptor dependent mechanisms. This poses the question whether neuronal activation of the ARC alters digestive function beside gastric acid secretion. In the present study we investigated whether CRF pathways in the ARC–PVN axis are involved in the modulation of colonic motility. First we examined the effect of an excitatory amino acid, kainate, microinjected into the ARC on colonic motility in anesthetized rats. Colonic motility was measured with a non-absorbable radioactive marker using the geometric center method. Kainate (120 pmol/rat) bilaterally microinjected into the ARC induced a significant stimulation of colonic propulsion. To assess the contribution of hypothalamic CRF to the effects of neuronal stimulation in the ARC on colonic motility we performed consecutive bilateral microinjections of an antagonist to CRF receptors into the PVN and the excitatory amino acid kainate into the ARC. Microinjection of the non-selective CRF receptor antagonist, astressin (100 ng), into the PVN abolished the stimulatory effect of neuronal activation in the ARC by kainate on colonic motor function. The data indicate that activation of neurons in the ARC stimulates colonic motility via CRF-receptor-mediated mechanism in the PVN and underlines the important role of the ARC–PVN circuit for the integrative CNS regulation of GI function.
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