Relation of aspirin failure to clinical outcome and to platelet response to aspirin in patients with acute myocardial infarction

Aspirin failure, defined as occurrence of an acute coronary syndrome despite aspirin use, has been associated with a higher cardiovascular risk profile and worse prognosis. Whether this phenomenon is a manifestation of patient characteristics or failure of adequate platelet inhibition by aspirin has never been studied. We evaluated 174 consecutive patients with acute myocardial infarction. Of them, 118 (68%) were aspirin naive and 56 (32%) were regarded as having aspirin failure. Platelet function was analyzed after ≥72 hours of aspirin therapy in all patients. Platelet reactivity was studied by light-transmitted aggregometry and under flow conditions. Six-month incidence of major adverse coronary events (death, recurrent acute coronary syndrome, and/or stroke) was determined. Those with aspirin failure were older (p = 0.002), more hypertensive (p <0.001), more hyperlipidemic (p <0.001), and more likely to have had a previous cardiovascular event and/or procedure (p <0.001). Cumulative 6-month major adverse coronary events were higher in the aspirin-failure group (14.3% vs 2.5% p <0.01). Patients with aspirin failure had lower arachidonic acid-induced platelet aggregation (32 ± 24 vs 45 ± 30, p = 0.003) after aspirin therapy compared to their aspirin-naive counterparts. However, this was not significant after adjusting for differences in baseline characteristics (p = 0.82). Similarly, there were no significant differences in adenosine diphosphate-induced platelet aggregation and platelet deposition under flow conditions. In conclusion, our results suggest that aspirin failure is merely a marker of higher-risk patient profiles and not a manifestation of inadequate platelet response to aspirin therapy.     

Dihydrotestosterone increases hippocampal N-methyl-D-aspartate binding but does not affect choline acetyltransferase cell number in the forebrain or choline transporter levels in the CA1 region of adult male rats

Testosterone, acting through its androgenic metabolite 5alpha-dihydrotestosterone (DHT), can increase dendritic spine density in the CA1 region of the male rat hippocampus. The mechanisms mediating this increase in spines are presently unknown. In female rats, estrogen (E) has been shown to increase spine density, which is in part mediated by increases in N-methyl-d-aspartate (NMDA) receptors in the CA1 region and cholinergic forebrain inputs to the hippocampus. Whether similar mechanisms are responsible for the DHT-induced increase in spines in the male remains to be determined. In the first experiment, we used [(3)H]glutamate NMDA receptor binding autoradiography to assess whether DHT-treated males had higher NMDA receptor levels in the CA1 region of the hippocampus, compared with oil-treated males. In the second set of experiments, we used choline acetyltransferase (ChAT) in situ hybridization and immunohistochemistry to assess whether DHT could affect ChAT cell number in the forebrain. We also investigated the effect of DHT on hemicholinium-3-sensitive choline transporter levels in the CA1 region of the male hippocampus. We found that DHT significantly increased NMDA receptor binding in the CA1 region of males but had no effect on ChAT cell number in the forebrain or hemicholinium-3-sensitive choline transporter protein levels in the CA1 region. These data indicate that, similar to E-induced spinogenesis in females, DHT-induced increases in spine formation in males may require increases in NMDA receptors. However, unlike E-treated females, these data suggest that DHT does not influence cholinergic inputs to the hippocampus.     

Differences in male–female ratios of Aedes albopictus (Diptera: Culicidae) following ultra-low volume adulticide applications

Suppression of Aedes albopictus populations is a substantial challenge for mosquito control programs globally because juveniles of this species are found in numerous kinds of domestic artificial containers that are difficult to detect, access, and eliminate. We conducted a multi-year assessment of the effect of different interventions to control Ae. albopictus near the northernmost geographic boundary of the species in temperate North America and deployed an array of BG-Sentinel traps for adult surveillance. Here we present the results of a comparative examination of adult sex ratios in urban and suburban areas, shifts in sex ratios after control interventions, and a discussion of the critical drivers of population dynamics of Ae. albopictus in our area. We collected significantly more male mosquitoes in urban as compared to suburban areas in June through September, but not in May (p < 0.001). The higher number of male mosquitoes in urban areas could be attributed to a higher number of larval habitats within a closer proximity of the surveillance traps and the lower flight dispersal of males. Following application of adulticides in urban areas, Ae. albopictus male populations were reduced by 88% on average, which was higher than the 69% reduction in female populations. The higher reduction of male mosquitoes could be attributed to the smaller body mass of the males and their higher susceptibility to adulticides. The results of this study are directly relevant to the development of suitable control strategies that depend on manipulation of males, such as the sterile insect technique. The results could also be used to refine mosquito abatement by providing more accurate methods to determine the need and timing of vector control.     

Variations in blood supply to the anterior interventricular septum: incidence and possible clinical importance.

The variations of the blood supply to the anterior interventricular septum in a series of 1,089 patients are described. Special attention has been given to variations and frequency of occurrence of the septal perforators originating from the left anterior descending artery. These variations may have clinical significance in this era of coronary angioplasty and coronary bypass surgery.     

Effects of rapid volume expansion on the right filling pressures after prosthetic valve surgery.

The effects of rapid intravascular volume expansion were studied in 12 patients, 4 to 14 years after single prosthetic heart valve replacement. The data observed showed a statistically significant mean difference before and after volume expansion of right atrial mean pressure and right ventricular end diastolic and pulmonary capillary pressures. However, right atrial and pulmonary capillary pressures equilibration was not detected. The right atrial pressure form showed abnormal variations during inspiration. Dip and plateau right ventricular diastolic pressure configuration was recorded in 6 patients after expansion, was absent in 2 and questionable in 4. A deep Y descent with an M-shaped right atrial pressure form was recorded in all 12 patients. The explanation for these phenomena is unclear. Thus, in the absence of pressure equilibration and clinical evidence of constriction, the abnormalities recorded during rapid volume expansion should be cautiously interpreted.     

Study of the drug release mechanism from tyrphostin AG-1295-loaded nanospheres by in situ and external sink methods.

The present study focused on in vitro release of polylactide-nanoencapsulated tyrphostin AG-1295, a potential agent for local therapy of restenosis. The drug was formulated in matrix-type nanoparticles, termed nanospheres (NS) using the nanoprecipitation method. AG-1295 is a model for low-molecular weight lipophilic compounds, the release behavior of which cannot be adequately characterized by existing methods. An in vitro release technique suitable for optimizing the nanoparticulate formulation release behavior was developed through a novel external sink method and an in situ release method utilizing the environmental sensitivity of the AG-1295 fluorescence spectrum. Similar tendencies were demonstrated by both methods in drug release studied as a function of selected NS preparation variables. The release properties of the drug fractions varying in their binding mode to the carrier particles were studied by the external sink method. The NS surface-adsorbed drug exhibited a significantly higher release rate compared to the drug entrapped in the polymeric matrix. The in situ release of the encapsulated drug was analyzed using the diffusion models of release from a matrix-type sphere. The release was shown to be a composite process, with a burst phase attributed largely to the rapid dissociation of the surface-bound AG-1295. The diffusion-controlled phase exhibited an alteration in kinetic pattern obviously due to the drug distribution between polymeric matrix compartments differing in their permeability. Drug in vitro release investigation may be effectively used to characterize the drug-carrier interaction and internal carrier structure in nanoparticulate formulations, as well as optimize the release behavior in respect to their therapeutic application.     

The in-vitro effect of fibrinogen, factor XIII and thrombin-activatable fibrinolysis inhibitor on clot formation and susceptibility to tissue plasminogen activator-induced fibrinolysis in hemodilution model

Patients suffering major traumatic or surgical bleeding are often exposed to hemodilution resulting in dilutional coagulopathy. The aim of this study was to evaluate in vitro the effects of fibrinogen, factor XIII and thrombin-activatable fibrinolysis inhibitor (TAFI) on clot formation and resistance to fibrinolysis in hemodilution conditions. Citrated whole blood from 36 healthy volunteers was diluted to 30 and 60% with lactated Ringer's solution. Blood samples were subsequently supplemented with fibrinogen, FXIII, TAFI or their combinations. Rotation thromboelastometry (ROTEM) in whole blood and thrombin generation in plasma were performed in the presence of CaCl? and tissue factor/EXTEM reagent, and fibrinolysis was induced by tissue plasminogen activator (tPA). Hemodilution was expressed by decrease of peak height in thrombin generation and α-angle and maximum clot firmness (MCF) in ROTEM. Fibrinogen, FXIII or TAFI did not correct the decrease in thrombin generation peak height. In ROTEM, spiking of diluted blood with fibrinogen stimulated clot propagation. In tPA-treated blood fibrinogen, FXIII and TAFI increased clot firmness and inhibited fibrinolysis. Stronger protection against fibrinolysis was achieved combining FXIII with TAFI. Hemodilution was associated with inhibition of thrombin generation; however, this effect was not sensitive to blood spiking with fibrinogen, FXIII and TAFI. In ROTEM, these hemostasis agents improved clot strength and decreased clot susceptibility to tPA in nondiluted and to more extent in diluted blood. The maximal protection against fibrinolysis was caused by TAFI. Combining FXIII with TAFI exerted synergistic inhibitory effect on fibrinolysis.     

Diversity,frequency and antifungal resistance of Candida species in patients with type 2 diabetes mellitus

Objective: To determine number, species of Candida and Candida resistance to antifungal therapy according to the metabolic control state and the associated salivary changes in patients with type 2 diabetes mellitus (DM2).

Materials and methods: Samples of non-stimulated saliva were collected from 52 patients with DM2. Salivary pH was measured and cultured on Sabouraud glucose agar and the values of CFU/ml were calculated. The species were presumptively identified using CHROMagar Candida^® plates, and identification was confirmed by polymerase chain reaction (PCR). C. albicans isolates were cultured on SGA tetracycline agar with nystatin and fluconazole diffusion disks to measure susceptibility.

Results: Sixty six percent of the yeasts isolated were Candida albicans, followed by C. glabrata (20.7%). In patients with decompensated DM2, there was an inverse association between HbA1c value and salivary pH. At higher levels of salivary acidification, a greater diversity and quantity of yeasts of the genus Candida were observed. With nystatin, higher inhibition was observed at lower pH.

Conclusions: The antifungal therapies could be more effective if it consider, qualitative salivary characteristics as pH, that could determine the susceptibility of species of Candida to at least to nystatin, which is the most used antifungal for treatment to oral candidiasis in patients with DM2.