The dynamics of the focal changes in the gastric mucosa of patients with chronic gastritis based on the data from a multiyear endoscopic observation in a polyclinic

Out of 1700 patients suffering from chronic gastritis, a group of 221 patients followed up for 6 to 14 years at an outpatient clinic was distinguished. Endoscopy and biopsy of gastric mucosa areas with focal lesions were carried out annually. 140 patients were discovered to have atrophic hyperplastic gastritis, 81 "complete" erosions". The lesions were of solitary or multiple character and were coupled with the other manifestations of chronic gastritis. Histology revealed different manifestations of chronic atrophic gastritis. 7.2% of the patients showed moderate dysplasia of the epithelium. The follow-up of focal hyperplasias established invariability of those formations or occurrence of the new ones in 89% of cases. In patients with "complete" erosions, such a course was recorded in 47% of cases whereas in the remainder, there was a decrease or complete disappearance of the sign. Dynamics of the histological appearance available in 28% of the patients, lay in atrophy enhancement and in the appearance of foci of intestinal metaplasia. In an equal number of cases, dysplasia of the epithelium was invariable; in some cases, it disappeared or else its intensity changed (within the framework of mild and medium degree).     

A Peer-Educator Network HIV Prevention Intervention Among Injection Drug Users: Results of a Randomized Controlled Trial in St. Petersburg, Russia

We evaluated the efficacy of a peer-educator network intervention as a strategy to reduce HIV acquisition among injection drug users (IDUs) and their drug and/or sexual networks. A randomized controlled trial was conducted in St. Petersburg, Russia among IDU index participants and their risk network participants. Network units were randomized to the control or experimental intervention. Only the experimental index participants received training sessions to communicate risk reduction techniques to their network members. Analysis includes 76 index and 84 network participants who were HIV uninfected. The main outcome measure was HIV sero-conversion. The incidence rates in the control and experimental groups were 19.57 (95 % CI 10.74–35.65) and 7.76 (95 % CI 3.51–17.19) cases per 100 p/y, respectively. The IRR was 0.41 (95 % CI 0.15–1.08) without a statistically significant difference between the two groups (log rank test statistic X² = 2.73, permutation p value = 0.16). Retention rate was 67 % with a third of the loss due to incarceration or death. The results show a promising trend that this strategy would be successful in reducing the acquisition of HIV among IDUs.     

Reversal of granulocyte adherence to nylon fibers using local anesthetic agents: possible application to filtration leukapheresis

The effects of the cationic anesthetic agents tetracaine and lidocaine on granulocyte function, morphology, and adherence to nylon fibers were studied in an attempt to improve current methods of granulocyte collection by filtration leukapheresis (FL). When dissolved in acid- citrate-dextrose (ACD) plasma, these drugs significantly increased granulocyte elution from the fibers in a dose-related fashion. Granulocytes exposed to tetracaine and lidocaine remained more than 95% viable, retained normal bactericidal capacity after the drugs were washed from the cells, and had preserved membrane integrity, as evidenced by the normal ultrastructural appearance of tetracaine- exposed cells and an absence of leakage of lysozyme or lactic dehydrogenase. Granulocytes eluted with the anesthetic agents were rounded in shape with a reduction in the number of filopodial cytoplasmic projections and a relative absence of cytoplasmic vacuolization when compared to granulocytes eluted with ACD plasma alone. Dose-related inhibition of phagocytosis and adherence, which was largely reversible after washing the granulocytes, was noted. Greater than 95% of the lidocaine could be removed from the eluate with a single centrifugation and resuspension, indicating that granulocytes prepared by FL with anesthetic-enhanced elution could be potentially transfusable.     

Platelets inhibit the induction of nitric oxide synthesis by interleukin-1 beta in vascular smooth muscle cells

We have investigated the role of platelets in regulating the hemostatic and vasomotor properties of vascular smooth muscle. Experiments were performed to examine the effect of the releasate from activated platelets on the production of nitric oxide from interleukin-1 beta (IL- 1 beta)-treated cultured rat aortic smooth muscle cells. Treatment of vascular smooth muscle cells with IL-1 beta resulted in significant accumulation of nitrite in the culture media and in marked elevation of intracellular cyclic guanosine monophosphate (GMP) levels. The releasate from collagen-aggregated platelets blocked the IL-1 beta- mediated production of nitrite and the accumulation of cyclic GMP in smooth muscle cells in a platelet number-dependent manner. In functional assays, the perfusates from columns containing IL-1 beta- treated smooth muscle cells relaxed detector blood vessels without endothelium and the addition of IL-1 beta-treated smooth muscle cells to suspensions of platelets inhibited their thrombin-induced aggregation. The simultaneous treatment of smooth muscle cells with IL- 1 beta and the platelet releasate abolished both the vasorelaxing activities of the perfusates and the inhibition of platelet aggregation. Platelet releasates treated with a neutralizing antibody to platelet-derived growth factor (PDGF) failed to block IL-1 beta- induced nitric oxide production by the smooth muscle cells, as measured by both biochemical and functional assays. The platelet releasate from a patient with gray platelet syndrome likewise failed to block IL-1 beta-induced nitrite release by smooth muscle cells. These results demonstrate that platelets downregulate the production of nitric oxide by IL-1 beta-treated vascular smooth muscle cells through the release of PDGF. This effect may represent a novel mechanism by which platelets regulate vasomotor tone and thrombus formation at sites of vascular injury.     

High-sensitivity heat-capacity measurements on Sr2RuO4 under uniaxial pressure

A key question regarding the unconventional superconductivity of Sr2RuO4 remains whether the order parameter is single- or two-component. Under a hypothesis of two-component superconductivity, uniaxial pressure is expected to lift their degeneracy, resulting in a split transition. The most direct and fundamental probe of a split transition is heat capacity. Here, we report measurement of heat capacity of samples subject to large and highly homogeneous uniaxial pressure. We place an upper limit on the heat-capacity signature of any second transition of a few percent of that of the primary superconducting transition. The normalized jump in heat capacity, ΔC/C, grows smoothly as a function of uniaxial pressure, favoring order parameters which are allowed to maximize in the same part of the Brillouin zone as the well-studied van Hove singularity. Thanks to the high precision of our measurements, these findings place stringent constraints on theories of the superconductivity of Sr2RuO4.

Obtaining a full understanding of the superconductivity of Sr2RuO4 is a core challenge for condensed-matter physics. Since soon after its discovery over a quarter of a century ago (1), the superconducting order parameter of Sr2RuO4 has been known to be unconventional (2, 3) and to condense from a well-understood and fairly simple quasi-two-dimensional Fermi liquid metallic state (4–7). Given the profound advances in theoretical techniques in recent decades a full understanding of its superconductivity is an important, and attainable, challenge for the field. The form of the wave-vector-dependent susceptibility of Sr2RuO4 leads to the prediction of a rich superconducting phase diagram in weak-coupling calculations which aim to perform a bias-free estimate of the condensation energies of different order parameters. A notable feature of the results is how close a number of different odd- and even-parity solutions are seen to be in energy (8–10). On the one hand, this emphasizes the potential of Sr2RuO4 as a test-bed material on which to refine the predictive capabilities of modern theories of unconventional superconductivity (11). On the other hand, realizing this potential will likely first require a conclusive experimental determination of which of the many possible order parameters wins out in the real material. This is a particularly exciting stage of the quest to complete this empirical determination, for reasons that we will now outline.For over 20 y the large majority of attention was paid to odd-parity order parameter candidates for Sr2RuO4 (12), because of NMR measurements of spin susceptibility in the superconducting state that seemed to be inconsistent with any even-parity order parameter (13). However, thanks to the discovery of a systematic error in the original NMR measurements (14, 15), that situation has now been more or less completely reversed. Taking into account the most recent measurements of the magnetic field dependence of the spin susceptibility (16), it seems clear that the order parameter must be even-parity or at least dominated by an even-parity component. The spin susceptibility results would be most easily describable in terms of a single-component, likely d-wave, order parameter, but recent thermodynamic evidence from ultrasound experiments is most straightforwardly interpreted in terms of an order parameter with two degenerate components (17, 18). Such order parameters do not of necessity break time-reversal symmetry, but they can, if the two degenerates have the appropriate phase relationship. In the context it is significant that long-standing muon-spin relaxation (μSR) (19, 20) and magneto-optic Kerr rotation measurements (21) have indicated time-reversal symmetry breaking in the superconducting state.To investigate any order parameter with two degenerate components, whether or not it breaks time-reversal symmetry, uniaxial pressure is a powerful probe because it can split the degeneracy, creating a split superconducting phase transition (22). In a significant experimental advance, the muon-spin relaxation experiments have recently been extended to high uniaxial pressures (23). In line with naive expectation, the temperature at which time-reversal symmetry is broken (TTRSB) splits from the main superconducting transition (Tc), with TTRSB remaining nearly pressure-independent while Tc increases under the application of the pressure. However, there has been a long-standing question about whether the Kerr and muon signals correspond to bulk thermodynamic transitions, so it is highly desirable to compare the new muon-spin relaxation data with those from a bulk thermodynamic probe. In this context, it is natural to look at heat capacity, because it has an intrinsic sensitivity to transitions within the superconducting state, as is well known from work on UPt3 (24, 25).     

Altered lysophosphatidic acid (LPA) receptor expression during hepatic regeneration in a mouse model of partial hepatectomy

Background

Hepatic regeneration requires coordinated signal transduction for efficient restoration of functional liver mass. This study sought to determine changes in lysophosphatidic acid (LPA) and LPA receptor (LPAR) 1–6 expression in regenerating liver following two-thirds partial hepatectomy (PHx).

Methods

Liver tissue and blood were collected from male C57BL/6 mice following PHx. Circulating LPA was measured by enzyme-linked immunosorbent assay (ELISA) and hepatic LPAR mRNA and protein expression were determined.

Results

Circulating LPA increased 72 h after PHx and remained significantly elevated for up to 7 days post-PHx. Analysis of LPAR expression after PHx demonstrated significant increases in LPAR1, LPAR3 and LPAR6 mRNA and protein in a time-dependent manner for up to 7 days post-PHx. Conversely, LPAR2, LPAR4 and LPAR5 mRNA were barely detected in normal liver and did not significantly change after PHx. Changes in LPAR1 expression were confined to non-parenchymal cells following PHx.

Conclusions

Liver regeneration following PHx is associated with significant changes in circulating LPA and hepatic LPAR1, LPAR3 and LPAR6 expression in a time- and cell-dependent manner. Furthermore, changes in LPA–LPAR post-PHx occur after the first round of hepatocyte division is complete.     

Pharmacokinetics and Biodistribution of Anastrozole in a Polymer-Containing Formulation

Pharmaceutical Chemistry Journal - A polymer-containing anastrozole formulation (PAF) in the form of micronized particles based on a copolymer of lactic and glycolic acids with a terminal carboxyl...