G protein-coupled receptor (GPR)40-dependent potentiation of insulin secretion in mouse islets is mediated by protein kinase D1.

AIMS/HYPOTHESIS: Activation of the G protein-coupled receptor (GPR)40 by long-chain fatty acids potentiates glucose-stimulated insulin secretion (GSIS) from pancreatic beta cells, and GPR40 agonists are in clinical development for type 2 diabetes therapy. GPR40 couples to the G protein subunit Gα(q/11) but the signalling cascade activated downstream is unknown. This study aimed to determine the mechanisms of GPR40-dependent potentiation of GSIS by fatty acids. METHODS: Insulin secretion in response to glucose, oleate or diacylglycerol (DAG) was assessed in dynamic perifusions and static incubations in islets from wild-type (WT) and Gpr40 (-/-) mice. Depolymerisation of filamentous actin (F-actin) was visualised by phalloidin staining and epifluorescence. Pharmacological and molecular approaches were used to ascertain the roles of protein kinase D (PKD) and protein kinase C delta in GPR40-mediated potentiation of GSIS. RESULTS: Oleate potentiates the second phase of GSIS, and this effect is largely dependent upon GPR40. Accordingly, oleate induces rapid F-actin remodelling in WT but not in Gpr40 (-/-) islets. Exogenous DAG potentiates GSIS in both WT and Gpr40 (-/-) islets. Oleate induces PKD phosphorylation at residues Ser-744/748 and Ser-916 in WT but not Gpr40 (-/-) islets. Importantly, oleate-induced F-actin depolymerisation and potentiation of GSIS are lost upon pharmacological inhibition of PKD1 or deletion of Prkd1. CONCLUSIONS/INTERPRETATION: We conclude that the signalling cascade downstream of GPR40 activation by fatty acids involves activation of PKD1, F-actin depolymerisation and potentiation of second-phase insulin secretion. These results provide important information on the mechanisms of action of GPR40, a novel drug target for type 2 diabetes.

Decreasing airborne contamination levels in high-risk hospital areas using a novel mobile air-treatment unit.

OBJECTIVE: To evaluate the performance of a new mobile air-treatment unit that uses nonthermal-plasma reactors for lowering the airborne bioburden in critical hospital environments and reducing the risk of nosocomial infection due to opportunistic airborne pathogens, such as Aspergillus fumigatus. METHODS: Tests were conducted in 2 different high-risk hospital areas: an operating room under simulated conditions and rooms hosting patients in a pediatric hematology ward. Operating room testing provided performance evaluations of removal rates for airborne contamination (ie, particles larger than 0.5 microm) and overall lowering of the airborne bioburden (ie, colony-forming units of total mesophilic flora and fungal flora per cubic meter of air). In the hematology service, opportunistic and nonpathogenic airborne fungal levels in a patient's room equipped with an air-treatment unit were compared to those in a control room. RESULTS: In an operating room with a volume of 118 m(3), the time required to lower the concentration of airborne particles larger than 0.5 microm by 90% was decreased from 12 minutes with the existing high-efficiency particulate air filtration system to less than 2 minutes with the units tested, with a 2-log decrease in the steady-state levels of such particles (P<.01). Concurrently, total airborne mesophilic flora concentrations dropped by a factor of 2, and the concentrations of fungal species were reduced to undetectable levels (P<.01). The 12-day test period in the hematology ward revealed a significant reduction in airborne fungus levels (P<.01), with average reductions of 75% for opportunistic species and 82% for nonpathogenic species. CONCLUSION: Our data indicate that the mobile, nonthermal-plasma air treatment unit tested in this study can rapidly reduce the levels of airborne particles and significantly lower the airborne bioburden in high-risk hospital environments.

Viscosity effects in foam drainage: Newtonian and non-newtonian foaming fluids.

We have studied the drainage of foams made from Newtonian and non-Newtonian solutions of different viscosities. Forced-drainage experiments first show that the behavior of Newtonian solutions and of shear-thinning ones (foaming solutions containing either Carbopol or Xanthan) are identical, provided one considers the actual viscosity corresponding to the shear rate found inside the foam. Second, for these fluids, a drainage regime transition occurs as the bulk viscosity is increased, illustrating a coupling between surface and bulk flow in the channels between bubbles. The properties of this transition appear different from the ones observed in previous works in which the interfacial viscoelasticity was varied. Finally, we show that foams made of solutions containing long flexible PolyEthylene Oxide (PEO) molecules counter-intuitively drain faster than foams made with Newtonian solutions of the same viscosity. Complementary experiments made with fluids having all the same viscosity but different responses to elongational stresses (PEO-based Boger fluids) suggest an important role of the elastic properties of the PEO solutions on the faster drainage.

A combined streaming-potential optical reflectometer for studying adsorption at the water/solid surface.

A novel in-situ streaming-potential optical reflectometry apparatus (SPOR) was constructed and utilized to probe the molecular architecture of aqueous adsorbates on a negatively charged silica surface. By combining optical reflectometry and electrokinetic streaming potentials, we measure simultaneously the adsorption density, gamma, and zeta potential, zeta, in a rectangular flow cell constructed with one transparent wall. Both dynamic and equilibrium measurements are possible, allowing the study of sorption kinetics and reversibility. Using SPOR, we investigate the adsorption of a classic nonionic surfactant (pentaethylene glycol monododecyl ether, C12E5), a simple cationic surfactant (hexadecyl trimethylammonium bromide, CTAB) of opposite charge to that of the substrate surface, and two cationic polyelectrolytes (poly(2-(dimethylamino)ethyl methacrylate), PDAEMA; (poly(propyl methacrylate) trimethylammonium chloride, MAPTAC). For the polyethylene oxide nonionic surfactant, bilayer adsorption is established above the critical micelle concentration (cmc) both from the adsorption amounts and from the interpretation of the observed zeta potentials. Near adsorption saturation, CTAB also forms bilayer structures on silica. Here, however, we observe a strong charge reversal of the surface. The SPOR data, along with Gouy-Chapman theory, permit assessment of the net ionization fraction of the CTAB bilayer at 10% so that most of the adsorbed CTAB molecules are counterion complexed. The adsorption of both C12E5 and CTAB is reversible. The adsorption of the cationic polymers, however, is completely irreversible to a solvent wash. As with CTAB, both PDAEMA and MAPTAC demonstrate strong charge reversal. For the polyelectrolyte molecules, however, the adsorbed layer is thin and flat. Here also, a Gouy-Chapman analysis shows that less than 20% of the adsorbed layer is ionized. Furthermore, the amount of charge reversal is inversely proportional to the Debye length in agreement with available theory. SPOR provides a new tool for elucidating aqueous adsorbate molecular structure at solid surfaces.

Adsorption of oppositely charged polyelectrolyte/surfactant complexes at the air/water interface: formation of interfacial gels.

The adsorption and complexation of polystyrene sulfonate (a highly charged anionic polyelectrolyte) and dodecyltrimethylammonium bromide (a cationic surfactant) at the air-water interface can lead to interfacial gels that strongly influence foam-film drainage and stability. The formation and characteristics of these gels have been studied by combining surface tension, ellipsometry, and foam-film drainage experiments. Simultaneously, the solution electromotive force is measured and used to track the polymer-surfactant interactions in the bulk solution. We find that surface gelation occurs above the critical aggregation concentration in solution but before bulk precipitation of the polymer-surfactant complexes. Furthermore, we reveal that strong readsorption of polymer-surfactant complexes occurs during the resolubilization of the precipitated complexes at high surfactant concentrations (i.e., >>critical micelle concentration). Seemingly overlooked in the past, this readsorption significantly influences the surface rheological properties and foam-film drainage of these systems.

Controlling droplet deposition with polymer additives

Controlling the impact of drops onto solid surfaces is important for a wide variey of coating and deposition processes--for example, the treatment of plants with herbicides and pesticides requires precise targeting in order to meet stringent toxicological regulations. However, the outer wax-like layer of the leaves is a non-wetting substrate that causes sprayed droplets to rebound; often less than 50% of the initial spray is retained by the plant. Although the impact and subsequent retraction of non-wetting aqueous drops on a hydrophobic surface have been the subjects of extensive experimental and theoretical work, non-newtonian rheological effects have not been considered in any detail. Here we report that, by adding very small amounts of a flexible polymer to the aqueous phase, we can inhibit droplet rebound on a hydrophobic surface and markedly improve deposition without significantly altering the shear viscosity of the solutions. Our results can be understood by taking into account the non-newtonian elongational viscosity, which provides a large resistance to drop retraction after impact, thereby suppressing droplet rebound.

Epidural corticosteroid injections for sciatica due to herniated nucleus pulposus.

BACKGROUND: Although epidural corticosteroid injections are commonly used for sciatica, their efficacy has not been established. METHODS: In a randomized, double-blind trial, we administered up to three epidural injections of methylprednisolone acetate (80 mg in 8 ml of isotonic saline) or isotonic saline (1 ml) to 158 patients with sciatica due to a herniated nucleus pulposus. All patients had Oswestry disability scores higher than 20 (on a scale of 1 to 100, with scores of 20 or less indicating minimal disability, and higher scores greater disability). RESULTS: At three weeks, the Oswestry score had improved by a mean of -8.0 in the methylprednisolone group and -5.5 in the placebo group (95 percent confidence interval for the difference, -7.1 to 2.2). Differences in improvements between the groups were not significant, except for improvements in the finger-to-floor distance (P=0.006) and sensory deficits (P=0.03), which were greater in the methylprednisolone group. After six weeks, the only significant difference was the improvement in leg pain, which was greater in the methylprednisolone group (P=0.03). After three months, there were no significant differences between the groups. The Oswestry score had improved by a mean of -17.3 in the methylprednisolone group and -15.4 in the placebo group (95 percent confidence interval for the difference, -9.3 to 5.4). At 12 months, the cumulative probability of back surgery was 25.8 percent in the methylprednisolone group and 24.8 percent in the placebo group (P=0.90). CONCLUSIONS: Although epidural injections of methylprednisolone may afford short-term improvement in leg pain and sensory deficits in patients with sciatica due to a herniated nucleus pulposus, this treatment offers no significant functional benefit, nor does it reduce the need for surgery.

Combination therapy with flutamide and castration (LHRH agonist or orchiectomy) in advanced prostate cancer: a marked improvement in response and survival.

Eighty-seven previously untreated patients with clinical stage D2 (bone metastases) prostate cancer have received the combination therapy with a pure antiandrogen and an LHRH agonist (or orchiectomy) as first treatment in a multicentre study for up to 34 months (average = 16.2 months). A positive objective response assessed according to the criteria of the US NPCP has been observed in all cases. Pain disappeared in all patients within 1 month and performance become normal in all (including 2 bedridden patients) within 4 months. Progression of the disease after a period of remission has been observed in only 8 patients. Only one patient has died from prostate cancer while 3 have died from other causes. The probability of continuing response and survival at 2 years for the patients who receive the combination treatment (Kaplan-Meier's method) is 81 and 91%, respectively. By contrast, in the randomized group who had orchiectomy alone, 4 of 7 have died from prostate cancer (P less than 0.05 as compared to combination therapy). In addition to a marked improvement in the remission rate and survival, combination therapy maintains a good quality of life, hot flashes and a decrease or loss of libido being the only side-effects.

[Legal protection of the mentally ill and the mentally retarded.]. / La protection légale des malades et déficients mentaux.

In this article the author describes the current legal system as it applies to the legal protection of the mentally ill and retarded. He speaks mainly of the laws and regulations which apply to every Quebec citizen; of the civil procedure code ; of the law for protection of the mentally ill, of the law on Public Curatorship; of the law on the Social Affairs commission and the regulations which define the role of the various organisations. He concludes by suggesting two things : the distribution of the texts of the laws and regulations to those concerned and the giving of courses on them to future practitioners.