Saliva Production and Esophageal Motility Influence Esophageal Acid Clearance Related to Post-reflux Swallow-Induced Peristaltic Wave.

BACKGROUND: The post-reflux swallow-induced peristaltic wave (PSPW) brings salivary bicarbonate to neutralize residual distal esophageal mucosal acidification. AIMS: To determine if reduced saliva production and esophageal body hypomotility would compromise PSPW-induced pH recovery in the distal esophagus. METHODS: In this multicenter retrospective cross-sectional study, patients with confirmed Sjogren's syndrome and scleroderma/mixed connective tissue disease (MCTD) who underwent high resolution manometry (HRM) and ambulatory pH-impedance monitoring off antisecretory therapy were retrospectively identified. Patients without these disorders undergoing HRM and pH-impedance monitoring for GERD symptoms were identified from the same time-period. Acid exposure time, numbers of reflux episodes and PSPW, pH recovery with PSPW, and HRM metrics were extracted. Univariate comparisons and multivariable analysis were performed to determine predictors of pH recovery with PSPW. RESULTS: Among Sjogren's syndrome (n = 34), scleroderma/MCTD (n = 14), and comparison patients with reflux symptoms (n = 96), the scleroderma/MCTD group had significantly higher AET, higher prevalence of hypomotility, lower detected reflux episodes, and very low numbers of PSPW (p ≤ 0.004 compared to other groups). There was no difference in pH-impedance metrics between Sjogren's syndrome, and comparison patients (p ≥ 0.481). Proportions with complete pH recovery with PSPW was lower in Sjogren's patients compared to comparison reflux patients (p = 0.009), predominantly in subsets with hypomotility (p < 0.001). On multivariable analysis, diagnosis of Sjogren's syndrome, scleroderma/MCTD or neither (p = 0.014) and esophageal hypomotility (p = 0.024) independently predicted lack of complete pH recovery with PSPW, while higher total reflux episodes trended (p = 0.051). CONCLUSIONS: Saliva production and motor function are both important in PSPW related pH recovery.

Natural external plastron mold of the Triassic turtle Proterochersis: An unusual mode of preservation.

Impressions of vertebrate bodies or their parts, such as trace fossils and natural molds of bones, are a valuable source of information about ancient faunas which may supplement the standard fossil record based on skeletal elements. Whereas trace fossils of animal activity are relatively common and actively studied within the field of ichnology, and natural impressions of internal or external surfaces are a frequent preservation mode in fossil invertebrates, natural molds of bones are comparatively rare and less extensively documented and discussed. Among them, internal molds (steinkerns) of turtle shells are a relatively well-known form of preservation, but the mechanisms and taphonomic prerequisites leading to their formation are poorly studied. External shell molds are even less represented in the literature. Herein, we describe a historic specimen of a natural external turtle plastron mold from the Triassic (Norian) Löwenstein Formation of Germany-a formation which also yielded a number of turtle steinkerns. The specimen is significant not only because it represents an unusual form of preservation, but also due to its remarkably large size and the presence of a potential shell pathology. Although it was initially interpreted as Proterochersis sp., the recent progress in the knowledge of proterochersid turtles leading to an increase in the number of known taxa within that group allows us to verify that assessment. We confirm that the specimen is morphologically consistent with the genus and tentatively identify it as Proterochersis robusta, the only representative of that genus from the Löwenstein Formation. We note, however, that its size exceeds the size observed thus far in Proterochersis robusta and fits within the range of Proterochersis porebensis from the Grabowa Formation of Poland. The marks interpreted as shell pathology are morphologically consistent with Karethraichnus lakkos-an ichnotaxon interpreted as a trace of ectoparasites, such as leeches. This may support the previously proposed interpretation of Proterochersis spp. as a semiaquatic turtle. Moreover, if the identification is correct, the specimen may represent a very rare case of a negative preservation of a named ichnotaxon. Finally, we discuss the taphonomy of the Löwenstein Formation turtles in comparison with other Triassic turtle-yielding formations which show no potential for the preservation of internal or external shell molds and propose a taphonomic model for the formation of such fossils.

Proximal esophageal impedance baseline increases the yield of impedance-pH and is associated with response to PPIs in chronic cough patients.

BACKGROUND: Chronic cough significantly impairs the quality of life. Although various studies focused on MNBI as assessed in the distal esophagus, scarce data are available on the clinical value of proximal measurements. AIM: To investigate the role of proximal MNBI in the workup of patients with chronic cough and its ability to predict PPI response. METHODS: Demographic, clinical, endoscopy findings, impedance-pH and HRM tracings from consecutive cough patients were evaluated. MNBI was calculated at proximal and distal esophagus. RESULTS: One hundred and sixty four patients were included. In addition to traditional variables, when considering also the PSPW index or MNBI at 3 cm or 15 cm, the proportion of patients with pathological impedance-pH monitoring significantly increased. 70/164 patients were responders, while 94 (57.3%) were non-responder to double PPI dose (p < 0.05). Patients with pathologic MNBI at 3 cm and/or 15 cm as well as those with pathologic PSPW index were characterized by a significantly higher proportion of responders than that observed among patients with normal impedance-pH variables (p < 0.001). The proportion of responders with pathological MNBI at 15 cm was significantly higher than the proportion of responders with pathological MNBI at 3 cm (82.8% vs. 64.3%, p < 0.05). At multivariable model, pathological MNBI at both 3 cm and 15 cm as well as PSPW index were associated with PPI responsiveness. The strongest association with PPI response was observed for MNBI at 15 cm. CONCLUSIONS: The assessment of MNBI at proximal esophagus increases the diagnostic yield of impedance-pH monitoring and may represent a useful predictor of PPI responsiveness in the cumbersome clinical setting of suspected reflux-related cough.

Chicago Classification v4.0 Stratifies Acid Burden and Abnormal Impedance-pH Variables Better Than Chicago Classification v3.0 Chicago Classification v4.0 and GERD.

INTRODUCTION: Gastroesophageal reflux disease (GERD) severity increases with esophageal body hypomotility, but the impact of Chicago Classification (CC) v4.0 criteria on GERD diagnosis is incompletely understood. METHODS: In patients with GERD evaluated with high-resolution manometry and pH-impedance monitoring, CCv3.0 and CCv4.0 diagnoses were compared. RESULTS: In 247 patients, hypomotility diagnosis decreased from 45.3% (CCv3.0) to 30.0% (CCv4.0, P < 0.001). In contrast, within patients with ineffective esophageal motility, proportions with pathological acid exposure increased from 38% (CCv3.0) to 88% (CCv4.0); baseline impedance and esophageal clearance demonstrated similar findings ( P < 0.05 for each comparison). DISCUSSION: CCv4.0 hypomotility criteria are more specific in supporting GERD evidence compared with CCv3.0.

Proximal esophageal impedance baseline increases the yield of impedance-pH monitoring for GERD diagnosis and is associated with heartburn response to PPI.

BACKGROUND: Impairment of esophageal mucosal integrity as assessed by low mean nocturnal baseline impedance (MNBI) measured in the distal esophagus increases the diagnostic yield of impedance-pH in patients with inconclusive GERD diagnosis as defined by Lyon criteria. AIM: To assess the diagnostic yield of MNBI measurement in the proximal esophagus, and its relationship with PPI response. METHODS: Expert review of off-therapy impedance-pH tracings from consecutive patients with heartburn, 80 responders and 80 non-responders to label-dose PPI. Data were compared to those from 36 healthy controls using ROC analysis. Multivariate analysis was performed to measure the strength of association of MNBI with PPI response. RESULTS: A threshold value of 2665 Ω was defined for proximal MNBI by ROC analysis, affording 91.7% sensitivity and 86.5% specificity. Proximal and distal MNBI were significantly lower in non-responder cases as compared to responders. Adding proximal MNBI positivity to pathologic (>6%) acid exposure time (AET) and positive symptom-reflux association, the proportion of patients with abnormal impedance-pH findings increased from 74/160 (46%) to 106/160 (66.3%) (p = 0.0016). Among the 12 patients with pathologic proximal MNBI as the only positive impedance-pH finding, 9 cases (75%) were PPI responders. According to multivariate analysis, AET and pathological distal and proximal MNBI were significantly associated with PPI response, the strongest association observed for proximal MNBI. CONCLUSIONS: Impedance baseline assessment in the proximal esophagus may increase the diagnostic yield of impedance-pH monitoring. Heartburn response to PPI is directly related to ultrastructural mucosal damage in the distal and in the proximal esophagus as well.

Anxiety correlates with excessive air swallowing and PPI refractoriness in patients with concomitant symptoms of GERD and functional dyspepsia.

BACKGROUND: Anxiety may exacerbate GERD and FD symptoms perception and reduce quality of life. As many as 50% of patients with GERD symptoms have incomplete relief with PPI therapy, and psychological factors may influence PPI responsiveness. AIM: The potential relationship between anxiety, excessive air swallowing, and PPI responsiveness was evaluated. METHODS: GERD patients with concomitant FD were prospectively evaluated. Validated structured questionnaires were used to evaluate anxiety, GERD, and FD symptoms. All patients were treated, within the previous year, with at least 8 weeks of standard dose PPI therapy. RESULTS: One hundred sixty-one patients were included. Frequency of non-responders in patients with moderate/severe anxiety was significantly higher compared to patients with mild anxiety (62.7% vs. 37.3%, p < 0.01). Patients with moderate/severe anxiety displayed a significantly higher mean FD symptoms score value compared to patients with mild anxiety. A significantly higher mean number of air swallows were observed in patients with moderate/severe anxiety. At ROC analysis, air swallows and mixed reflux episodes were significantly associated with the presence of PPI refractoriness (AUC: 0.725, 95% CI: 0.645-0.805 and 0.768, 0.692-0.843). According to univariate analysis, an abnormal number of air swallows, mixed reflux episodes and presence of moderate/severe anxiety was significantly associated with PPI refractoriness. CONCLUSION: Our results, if confirmed in in a larger, prospective clinical and therapeutic study, demonstrate the usefulness of an up-front evaluation with anxiety questionnaire and esophageal testing in patients with a broad spectrum of upper gastrointestinal symptoms who fail to respond to PPI treatment, supporting the option of alternative treatment modalities.

Oxyprenylated Secondary Metabolites as Modulators of Lipid and Sugar Metabolism.

O-Prenylcoumarins (3,3-dimethylallyl, geranyl-, farnesyl- and related biosynthetic derivatives) represent a class of rarely occurring natural compounds. Most of these secondary metabolites have been obtained from plant species belonging to the Rutaceae, Apiaceae, and Fabaceae families, and from fungi, and bacteria. In the last two decades, prenyloxycoumarins have been found to possess great potential in terms of pharmacological activities. The aim of this comprehensive review is to make a survey of the so far reported literature citations about these valuable phytochemicals and structurally related compounds about their modulatory properties of lipid and sugar metabolism. Literature data have been acquired from the main Internet database. Several oxyprenylated secondary metabolites have been surveyed. Among these, prenyloxycoumarins represented the main group displaying valuable effects as modulators of lipid and sugar metabolism. The title phytochemicals have been found in common fruits and vegetables already known to have beneficial effects, thus enforcing the nutraceutical role of these food plants. All compounds outlined in the present review article have a great potential in future for the prevention and management of acute and chronic metabolic disorders.

An improved method for the isolation of amarogentin, the bitter principle of yellow gentian roots.

Amarogentin is well known to be among the most bitter naturally occurring compound. Either as an individual one or extracts, amarogentin is used as a food additive and as a dietary supplement. The aim of the present investigation is to set-up a convenient process to selectively isolate amarogentin from the ethanolic roots extract of Gentiana lutea. The process consisted in the treatment of an aqueous suspension of such an extract with a panel of 21 solid inorganic / organic sorbents followed by filtration, desorption, and high performance liquid chromatography (HPLC) analyses. Among the solid materials tested, those containing Mg+2 in the frame of a lamellar structure provided very good adsorption yields in the range 86.4% - 99.9% (p < 0.05 at Student's t-test). The method we set up could be in principle useful to obtain a pure nature-derived food additive to provide bitter taste to foods and beverages.

Semisynthesis of Selenoauraptene.

Selenium-containing compounds are gaining more and more interest due to their valuable and promising pharmacological properties, mainly as anticancer and antioxidant agents. Ebselen, the up to now only approved drugs, is well known to possess very good glutathione peroxidase mimicking effects. To date, the most of efforts have been directed to build pure synthetic Se containing molecules, while less attention have been devoted to Se-based semisynthetic products resembling natural compounds like terpenes, polyphenols, and alkaloids. The aim of this short communication is to report the synthesis of the first example of a Se-phenylpropanoids, namely selenoauraptene, containing a selenogeranyl side chain in position 7 of the umbelliferone core. The key step was the Newman-Kwart rearrangement to obtain a selenocarbamate in which the Se atom was directly attached to umbelliferone (replacing its 7-OH function) followed by hydrolysis to get diumbelliferyl diselenide, which was finally easily converted to the desired Se-geranyl derivative in quite a good overall yield (28.5%). The synthesized adduct displayed a greater antioxidant and a radical scavenger in vitro activity than parent auraptene. The procedure we describe herein, to the best of our knowledge for the first time in the literature, represents an easy-to-handle method for the synthesis of a wide array of seleno analogues of naturally occurring biologically active oxyprenylated secondary metabolites.

Pre-concentration of active principles from different varieties of Camellia sinensis extracts by solid sorbents.

In this article we studied the phytochemical composition of leaves extracts of different varieties of Camellia sinensis(L.) Kuntze after treatment with 16 selected solid sorbents (namely hydrotalcites, magnesium oxide and hydroxide, zirconium phosphates, and phyllosilicates). The pre-concentration and selective adsorption of the main active principles of this food and medicinal plant [e.g. gallic acid, (-)-epicatechin, (-)-epicatechin gallate, and caffeine] were investigated. The quantities of phytochemicals adsorbed by solids were measured by HPLC analysis, coupled to photodiode array detection and calculated as the difference between the quantities in the parent untreated extracts and those recorded in the filtrates. Caffeine was selectively adsorbed by bentonite to a large extent, while for the remaining phytochemicals different patterns were recorded depending on the type of leaves extract. A comparison with pure chemicals revealed a strong effect of the phytocomplex composition on the adsorption yields. The methodology outlined herein may be useful to obtain tea extracts enriched in selective active principles also for industrial scopes.

7-Isopentenyloxycoumarin: What Is New across the Last Decade.

7-Isopentenyloxycoumarin is among the most widespread naturally occurring prenyloxy umbelliferone derivatives. This secondary metabolite of mixed biosynthetic origin has been typically isolated from plants belonging to several genera of the Rutaceae and Apiaceae families, comprising widely used medicinal plants and in general plants with beneficial effects on human welfare, as well as edible fruits and vegetables. Although known for quite a long time (more than 50 years), only in the last two decades has this natural compound been revealed to exert powerful and promising pharmacological properties, such as active cancer chemopreventive, antibacterial, antiprotozoal, antifungal, anti-inflammatory, neuroprotective, and antioxidant properties, among the activities best outlined in the recent literature. The aim of this comprehensive miniature review article is to detail the novel natural sources and the effects described during the last decade for 7-isopentenyloxycoumarin and what has been reported on the mechanisms of action underlying the observed biological activities of this oxyprenylated secondary metabolite. In view of the herein described data, suggestions on how to address future research on the abovementioned natural product and structurally related derivatives in the best ways according to the authors will be also provided.

Solid phase adsorption of anthraquinones from plant extracts by lamellar solids.

Solid phase extraction is nowadays a well validated and powerful technique applicable to complex matrices like plant extracts and phytocomplexes. This process provides concentration and/or purification of selected secondary metabolites from these matrices for subsequent analysis and isolation. In this research article sixteen lamellar solids, comprising layered structures (hydrotalcites, zirconium phosphates, magnesium hydroxide), magnesium oxide, and the phyllosilicates talc and bentonite were investigated for their capacity and performance to selectively adsorb five naturally occurring and widespread anthraquinones (aloe, aloe-emodin, rhein, chrysophanol, and physcion) contained in three ethanolic extracts of well known plants with purgative effects (frangula, senna, and rhubarb). Ethanolic solutions of extracts from these species were vigorously magnetically stirred with fixed quantities of each solid support at room temperature for 1 h. Subsequent HPLC analysis, coupled to photodiode array detection, revealed that, among the solids tested, the hydrotalcite zinc aluminum oleate and magnesium aluminum azelate and magnesium oxide were largely the most effective to this concern allowing to recover anthraquinones (all or some) in good to excellent percentages. Another interesting result was the selective and total removal of rhein by some sorbents from senna and rhubarb extracts. Sorbents were also recyclable and could be re-used to accomplish additional steps without appreciable loss of adsorption capacity. The application of the title solid inorganic and mixed inorganic/organic supports for the selective adsorption and concentration in the solid phase of anthraquinones from commonly used laxative plant species is reported herein for the first time.