Development of immune memory to glial brain tumors after tumor regression induced by immunotherapeutic Toll-like receptor 7/8 activation

The efficacy of immunotherapeutic TLR7/8 activation by resiquimod (R848) was evaluated in vivo, in the CNS-1 rat glioma model syngeneic to Lewis rats. The immune treatment was compared with cytotoxic cyclophosphamide chemotherapy, and as well, was compared with the combination cytotoxic and immunotherapeutic treatments. We found that parenteral treatment with the TLR7/8 agonist, resiquimod, eventually induced complete tumor regression of CNS-1 glioblastoma tumors in Lewis rats. Cyclophosphamide (CY) treatment also resulted in dramatic CNS-1 remission, while the combined treatment showed similar antitumor effects. The resiquimod efficacy appeared not to be associated with direct injury to CNS-1 growth, while CY proved to exert tumoricidal cytotoxicity to the tumor cells. Rats that were cured by treatment with the innate immune response modifier resiquimod proved to be fully immune to secondary CNS-1 tumor rechallenge. They all remained tumor-free and survived. In contrast, rats that controlled CNS-1 tumor growth as a result of CY treatment did not develop immune memory, as demonstrated by their failure to reject a secondary CNS-1 tumor challenge; they showed a concomittant outgrowth of the primary tumor upon secondary tumor exposure. Rechallenge of rats that initially contained tumor growth by combination chemo-immunotherapy also failed to reject secondary tumor challenge, indicating that the cytotoxic effect of the CY likely extended to the endogenous memory immune cells as well as to the tumor. These data demonstrate strong therapeutic antitumor efficacy for the immune response modifier resiquimod leading to immunological memory, and suggest that CY treatment, although effective as chemotherapeutic agent, may be deleterious to maintenance of long-term antitumor immune memory. These data also highlight the importance of the sequence in which a multi-modal therapy is administered

Micropropagation of Ilex khasiana, a critically endangered and endemic holly of Northeast India

The paper describes in vitro techniques for mass propagation of IIex khasiana, a rare and critically endangered holly endemic to Khasi Hills Hills of Meghalaya, India. The approach will help conserve I. khasiana and other endangered species

Whale, whale, everywhere: increasing abundance of western South Atlantic humpback whales (Megaptera novaeangliae) in their wintering grounds

The western South Atlantic (WSA) humpback whale population inhabits the coast of Brazil during the breeding and calving season in winter and spring. This population was depleted to near extinction by whaling in the mid-twentieth century. Despite recent signs of recovery, increasing coastal and offshore development pose potential threats to these animals. Therefore, continuous monitoring is needed to assess population status and support conservation strategies. The aim of this work was to present ship-based line-transect estimates of abundance for humpback whales in their WSA breeding ground and to investigate potential changes in population size. Two cruises surveyed the coast of Brazil during August-September in 2008 and 2012. The area surveyed in 2008 corresponded to the currently recognized population breeding area; effort in 2012 was limited due to unfavorable weather conditions. WSA humpback whale population size in 2008 was estimated at 16,410 (CV = 0.228, 95% CI = 10,563–25,495) animals. In order to compare abundance between 2008 and 2012, estimates for the area between Salvador and Cabo Frio, which were consistently covered in the two years, were computed at 15,332 (CV = 0.243, 95% CI = 9,595–24,500) and 19,429 (CV = 0.101, 95% CI = 15,958–23,654) whales, respectively. The difference in the two estimates represents an increase of 26.7% in whale numbers in a 4-year period. The estimated abundance for 2008 is considered the most robust for the WSA humpback whale population because the ship survey conducted in that year minimized bias from various sources. Results presented here indicate that in 2008, the WSA humpback whale population was at least around 60% of its estimated pre-modern whaling abundance and that it may recover to its pre-exploitation size sooner than previously estimated.Publisher PDFPeer reviewe

A Sol-Gel/Solvothermal Synthetic Approach to Titania Nanoparticles for Raman Thermometry

The accurate determination of the local temperature is one of the most important challenges in the field of nanotechnology and nanomedicine. For this purpose, different techniques and materials have been extensively studied in order to identify both the best-performing materials and the techniques with greatest sensitivity. In this study, the Raman technique was exploited for the determination of the local temperature as a non-contact technique and titania nanoparticles (NPs) were tested as nanothermometer Raman active material. Biocompatible titania NPs were synthesized following a combination of sol-gel and solvothermal green synthesis approaches, with the aim of obtaining pure anatase samples. In particular, the optimization of three different synthesis protocols allowed materials to be obtained with well-defined crystallite dimensions and good control over the final morphology and dispersibility. TiO2 powders were characterized by X-ray diffraction (XRD) analyses and room-temperature Raman measurements, to confirm that the synthesized samples were single-phase anatase titania, and using SEM measurements, which clearly showed the nanometric dimension of the NPs. Stokes and anti-Stokes Raman measurements were collected, with the excitation laser at 514.5 nm (CW Ar/Kr ion laser), in the temperature range of 293–323 K, a range of interest for biological applications. The power of the laser was carefully chosen in order to avoid possible heating due to the laser irradiation. The data support the possibility of evaluating the local temperature and show that TiO2 NPs possess high sensitivity and low uncertainty in the range of a few degrees as a Raman nanothermometer material

Calcium uptake during insulin-aggravated ischemic myocardial contracture in the rat heart

Perfusion of isolated, nondiabetic rat hearts with high concentrations of regular insulin (10 mU/ml) produced earlier onset of myocardial contracture during ischemia than control perfusions without insulin. High insulin concentrations also increased total myocardial calcium content (p < .001) and myocardial Ca-45 uptake postischemia (p < .05). Insulin perfusion before ischemia did not enhance calcium uptake. These results support the hypothesis that insulin may increase calcium movement across myocardial cell membranes, which may lead to increased ischemic contracture. Insulin-aggravated myocardial ischemia in cardiothoracic surgery and cardiac resuscitation deserves further investigation

Insulin worsens ischemia-induced myocardial contracture in the isolated rat heart

We used a modification of Langendorffs isolated perfused nonworking rat-heart model to study the effects of diabetes, insulin-treated diabetes, and hyperinsulinemia on left ventricular pressure, force of ventricular contraction, and myocardial contracture, before, during, and after 20 min of complete normothermic global ischemia. Untreated diabetic rat hearts behaved the same as normal hearts, but insulin-treated diabetic hearts had more ischemic and postischeimic contracture (p < .01), and less return of left ventricular function. Chronic insulin treatment potentiated ischemic contracture in diabetic and nondiabetic rat hearts. These results support the hypotheses that insulin can increase Ca actin-myosin ATPase activity, and increase the affinity of myofibrillar receptors for calcium, which may lead to increased ischemia contracture. Insulin as a risk factors in myocardial ischemia, cardiothoracic surgery and cardiac resuscitation, and other pathogenetic factors of “stone heart‘’ development, deserve further investigation