Effect of cisapride on functional dyspepsia in patients with and without histological gastritis: A double-blind placebo-controlled trial

In the present double-blind placebo-controlled study the effect of cisapride on functional dyspepsia was evaluated in patients with and without histological gastritis. Patients with functional dyspepsia and whose symptoms persisted after a 2 week run-in period with antacid treatment were randomized to receive cisapride (10 mg) or matching placebo three times daily for 4 weeks. Symptoms of epigastric pain, bloating, nausea, belching, early satiety and heartburn were graded on a four-point scale based on patients’ feedback and diary card recording. A global response was also formulated by the investigators. One hundred and four patients entered the study and 76 completed the trial, comprising 36 patients with histological gastritis and 40 patients without gastritis. Symptom scores in both gastritis and non-gastritis groups were significantly improved by both cisapride and placebo; however, the improvement was not statistically different between the two treatment groups. Cisapride produced a good or better global response in 58% of subjects with histological gastritis and in 53% of subjects without gastritis compared with 47% and 52%, respectively, of patients on placebo; this difference was not statistically significant. Gastric histology did not influence the effect of cisapride on the symptoms of functional dyspepsia.     

Prevalence of periodontitis in individuals with human leukocyte antigens (HLA) A9, B15, A2, and B5

Objective

Human leukocyte antigens (HLA) have been associated with periodontitis. Previous studies revealed HLA-A9 and HLA-B15 as potential susceptibility factors, while HLA-A2 and HLA-B5 might have protective effects. The aim of the study was to verify these associations in a group of HLA-typed blood donors with previously unknown periodontal status.

Materials and methods

In four German centers, 140 blood donors with known HLA class I status were enrolled and allocated to the following five groups: HLA-A9 (N = 24), HLA-B15 (N = 20), HLA-A2 (N = 30), HLA-B5 (N = 26), and controls (N = 40). Periodontal examination included the measurement of probing depths (PDs), clinical attachment level (CAL), bleeding on probing (BOP), and community periodontal index of treatment needs (CPITN).

Results

Carriers with HLA-A9 and HLA-B15 had higher values of mean PD (P < 0.0001), CAL (P < 0.0001), and BOP (P < 0.002) as well as sites with PD and CAL with ≥4 and ≥6 mm (P < 0.0003), respectively, than controls. Multiple regression analyses revealed HLA-A9, HLA-B15, and smoking as risk indicators for moderate to severe (CPITN 3–4; odds ratio (OR): 66.7, 15.3, and 5.1) and severe (CPITN 4; OR: 6.6, 7.4, and 3.8) periodontitis. HLA-A2 and HLA-B5 did not show any relevant associations.

Conclusion

The present data support a role of HLA-A9 and HLA-B15 as susceptibility factors for periodontitis, whereas HLA-A2 and HLA-B5 could not be confirmed as resistance factors.

Clinical relevance

Both HLA antigens A9 and B15 are potential candidates for periodontal risk assessment.

     

Platelet coagulation factor Va: the major secretory platelet phosphoprotein

Platelet-derived coagulation factor Va is the primary secreted substrate for a thrombin-stimulation-dependent platelet kinase. Human platelet factor Va, consisting of a molecular weight (M(r)) 105,000 heavy chain and an M(r) 74,000 light chain, incorporates phosphate in at least two sites on the light chain. Phosphorylated factor Va represents 50% of the secreted protein-associated phosphate. This modification occurs exclusively at serine residues and is inhibited by H-7 and staurosporine, which suggests a protein kinase C (PKC)-mediated event. Purified plasma factor V and Va are phosphorylated in the light chain region by rat brain PKC. The activity of platelet factor Va in prothrombinase on platelets is not altered when phosphorylation is inhibited by staurosporine. Plasma-derived factor Va in the presence of thrombin stimulated platelets is phosphorylated on both the heavy chain and the light chain. Plasma factor V and factor Va heavy chain phosphorylation occurs without light chain phosphorylation in the presence of added 32P gamma-ATP and non-stimulated or collagen- stimulated platelets or casein kinase II. This differential phosphorylation of factor Va heavy and light chain shows two independent platelet kinase activities that act on factor Va. The heavy chain factor V/Va kinase activity is similar to casein kinase II, which we have demonstrated previously to act on factor Va and accelerate activated protein C inactivation of the cofactor. Our data show platelet-dependent phosphorylation of platelet and plasma factor V and Va resulting in significant covalent modifications of the cofactor. These modifications may play a role in directing the extracellular distribution of factor V and factor Va.     

Ocean fronts drive marine fishery production and biogeochemical cycling

Long-term changes in nutrient supply and primary production reportedly foreshadow substantial declines in global marine fishery production. These declines combined with current overfishing, habitat degradation, and pollution paint a grim picture for the future of marine fisheries and ecosystems. However, current models forecasting such declines do not account for the effects of ocean fronts as biogeochemical hotspots. Here we apply a fundamental technique from fluid dynamics to an ecosystem model to show how fronts increase total ecosystem biomass, explain fishery production, cause regime shifts, and contribute significantly to global biogeochemical budgets by channeling nutrients through alternate trophic pathways. We then illustrate how ocean fronts affect fishery abundance and yield, using long-term records of anchovy–sardine regimes and salmon abundances in the California Current. These results elucidate the fundamental importance of biophysical coupling as a driver of bottom–up vs. top–down regulation and high productivity in marine ecosystems.Globally, marine primary production is considered to set the limits of fishery production (1), drive ecosystem functioning (2), and contribute substantially to biogeochemical cycles (3). Recent evidence of increased ocean temperatures (4, 5) and declines in global nutrient supply and primary production (6), combined with overfishing and other increasing human demands on the ocean (7–9), therefore raises significant concerns about fishery sustainability, ecosystem health, and maintaining global biogeochemical cycles (10). However, the degree of patchiness, instead of total biomass, may be the primary regulator of marine production and food web structure (11–16). Fronts in the ocean are boundaries between distinct water masses with sharp gradients in temperature or salinity (density) that can increase patchiness through flow convergence and, for density fronts, increase vertical mixing and nutrient supply (11, 17). Due to flow convergence at fronts, the spatiotemporal overlap of prey and predators can be immense, leading to a cascade of impacts across multiple scales from local prey size structure to global biogeochemical fluxes (11–13). However, the effects of fronts as fishery productivity and biogeochemical cycling hotspots have not been included in models that assess fisheries production and ecosystem health (18) or addressed at scales (tens to hundreds of kilometers) relevant to climate change (19).Here we use an ecosystem model to explore why fronts appear to have a strong influence on marine fishery production and biogeochemical cycling. Existing ecosystem models currently account only for the mean concentration of predator and prey with relatively large grid cells (20). In a simple case of a single autotrophic prey (A) and a single heterotrophic predator (B) the governing equations aredAdt=μaNA−gAB−maAdBdt=gμbAB−mbB.[1]These equations describe the change in biomass of predator and prey relative to nutrient supply (N), intrinsic growth (μ), grazing (g), and mortality (m) rates with a reactive term, gμ_zAB, coupling the two equations, and the mortality terms, m_aA and m_bB, represent the contribution of the interaction to biogeochemical cycling.In the ocean, concentrations of prey and predator are typically very low, and consequently, the production term in an ecosystem model will be even lower because it depends on the concentration of both (Fig. 1A). However, near fronts and other regions of sharp ocean gradients, the covariance of prey and predators is driven by (i) fluid dynamic processes that concentrate or disperse organisms (convergence/divergence, confluence/diffluence, mixing) and (ii) species-specific behaviors (11). Predator–prey covariance at fronts can be orders of magnitude higher than mean oceanic values (Fig. 1B and Fig. 1B). The decomposition results in an additional term, ?A^′B^′?, that represents the influence of the spatial covariance of prey and predator on the trophic dynamics of the ecosystem and imposes a similar closure problem to the dynamic equations.Open in a separate windowFig. 1.Effects of spatial covariance between predators and prey. (A) Evenly dispersed condition currently assumed in models. (B) Highly aggregated condition representative of most ocean environments. (C) Magnitude of the effect of spatial covariance on species production.

Table 1.

ζ_AB estimated from observations in available literature for multiple trophic interaction

Studies on the structure of bovine factor V by scanning transmission electron microscopy

We studied purified bovine factor V (mol wt 330,000) by scanning transmission electron microscopy (STEM) of freeze-dried unstained or negatively contrasted preparations. Freeze-dried molecules revealed discrete shapes ranging from roughly spheroidal (100 to 120 nm) to oblong (140 to 200 nm in length X 50 to 100 nm in width). Oblong shapes could often be resolved into two or three distinct domains, ranging from 60 to 100 nm in diameter. A "satellite" nodular structure (30 to 50 nm in diameter) connected to the main molecule by a thin stalk (approximately 10 nm wide) up to 80 nm in length was occasionally seen. Glutaraldehyde-treated preparations yielded the same shapes as were seen in unfixed preparations but revealed better definition of submolecular features and "satellite" nodules. STEM mass analysis confirmed that each of the different shapes represented a monomolecular form of factor V. Negatively stained images revealed objects having the same general shapes as freeze-dried molecules, although greater detail was evident. Some images suggested that molecules consist of five or more discrete parts. Taken together, these observations indicate that factor V molecules are multidomainal, flexible structures that tend to have an irregular oblong shape with an axial ratio between 3:2 and 2:1.