Stimuli Responsive In Situ Gelling Systems Loaded with PLGA Nanoparticles of Moxifloxacin Hydrochloride for Effective Treatment of Periodontitis.

The objectives of the present research work were systematic development of novel in situ gel formulation containing nanoparticles for localised delivery of moxifloxacin against bacterial periodontitis. PLGA nanoparticles were prepared and optimised in a systematic manner. Factor screening was performed with the help of half-factorial design to identify the influential factors, while response surface optimisation of the nanoparticles was conducted using central composite design. The optimum nanoparticle formulation was chosen on the basis of lower particle size, higher drug entrapment and controlled drug release characteristics up to 1 week time period, while the optimum in situ gel was selected on the basis of faster gelling and higher viscosity and gel strength properties for improved retention in the periodontium. In vivo histopathological studies and in vivo gamma scintigraphy studies revealed the extended release, superior efficacy and enhanced retention of nanoparticle-loaded in situ gelling system. Results obtained from in vivo histopathological studies after 1 week treatment with in situ gel formulation containing nanoparticles of moxifloxacin were found to be better than with 3 weeks treatment of marketed gel formulation. Overall, the studies ratify successful development of an effective site-specific drug delivery system with enhanced biopharmaceutical attributes for the periodontitis treatment.

Administration of antioxidants in cancer: debate of the decade.

Several randomized clinical trials have divulged that administration of antioxidants during chemotherapy decreases the effectiveness of treatment. Hence, the characteristic feature of this article is extensive assessment of putative benefits and potential risks of natural and synthetic antioxidant supplementation, administered with chemotherapy, based upon the available preclinical and clinical data. After analyzing mixed results, it was concluded that current FDA guidelines should be followed before supplementing antioxidants during cytotoxic treatment. Nevertheless, contradictory experimental animal models opposing human clinical trials discourage the concurrent administration of antioxidants ostensibly owing to the possibility of tumor protection and reduced survival.

Climate-driven uncertainties in modeling terrestrial gross primary production: a site level to global-scale analysis.

We used a land surface model to quantify the causes and extents of biases in terrestrial gross primary production (GPP) due to the use of meteorological reanalysis datasets. We first calibrated the model using meteorology and eddy covariance data from 25 flux tower sites ranging from the tropics to the northern high latitudes and subsequently repeated the site simulations using two reanalysis datasets: NCEP/NCAR and CRUNCEP. The results show that at most sites, the reanalysis-driven GPP bias was significantly positive with respect to the observed meteorology-driven simulations. Notably, the absolute GPP bias was highest at the tropical evergreen tree sites, averaging up to ca. 0.45 kg C m(-2)  yr(-1) across sites (ca. 15% of site level GPP). At the northern mid-/high-latitude broadleaf deciduous and the needleleaf evergreen tree sites, the corresponding annual GPP biases were up to 20%. For the nontree sites, average annual biases of up to ca. 20-30% were simulated within savanna, grassland, and shrubland vegetation types. At the tree sites, the biases in short-wave radiation and humidity strongly influenced the GPP biases, while the nontree sites were more affected by biases in factors controlling water stress (precipitation, humidity, and air temperature). In this study, we also discuss the influence of seasonal patterns of meteorological biases on GPP. Finally, using model simulations for the global land surface, we discuss the potential impacts of site-level reanalysis-driven biases on the global estimates of GPP. In a broader context, our results can have important consequences on other terrestrial ecosystem fluxes (e.g., net primary production, net ecosystem production, energy/water fluxes) and reservoirs (e.g., soil carbon stocks). In a complementary study (Barman et al., ), we extend the present analysis for latent and sensible heat fluxes, thus consistently integrating the analysis of climate-driven uncertainties in carbon, energy, and water fluxes using a single modeling framework.

Total rod ERG suppression with high dose compassionate Fenretinide usage.

Fenretinide is a synthetic retinoid that interferes with the attachment of retinol to retinol binding protein. It may inhibit accumulation of A2E and lipofuscin, and is proposed as therapy for Stargardt disease. It is currently used for cancer therapy, and mild depression of rod function and dark adaptation is a side effect at standard dosage. We studied two youngsters (aged between 12 and 13) receiving high doses as compassionate treatment for neuroblastoma: 800 mg daily for 1 out of every 3 weeks, for roughly 2 years. Goldmann-Weekers dark adaptometry, ISCEV standard ERG and mfERG were performed, and blood was analyzed for vitamin A. Neither child complained of night blindness or showed retinal fundus abnormalities. On initial exam, dark adaptation thresholds were elevated by 3 log units, and there were no detectable rod ERG responses. However, cone responses and mfERG were normal. Retesting one subject 3 months after stopping the drug revealed normal rod thresholds (slightly delayed) and low normal rod ERG responses. Serum vitamin A levels were normal from both subjects, but there is no record of whether the samples were drawn during cycles on or off drug. Our study demonstrates that high dose Fenretinide can suppress rod function quite completely, although serum vitamin A and rod function apparently return to normal or near normal levels rapidly once the drug is stopped. It is intriguing that cone function and access to vitamin A seems largely independent of Fenretinide effects on retinol availability.

Role and differential expression of calpastatin mRNA and protein in cultured cardiomyocytes exposed to hypoxic stress.

We previously proposed that the calpain-mediated proteolytic pathway is activated in cultured cardiomyocytes following exposure to hypoxia (Mol Cell Biochem 214: 47, 2000). The potential role of calpastatin, the endogenous specific inhibitor of calpain, and its expression in the hypoxic state were investigated here. Hypoxia induced the expression of two calpastatin and multiple VEGF splice variants. Although cardiomyocytes and fibroblasts responded to hypoxia differentially, both cell types exhibited hypoxia-induced calpastatin transcription. The two functional calpastatin splice variants encoding the 593- and 654-amino acid calpastatin isoforms differed only in their N-terminal leader domain sequences. In spite of the increased mRNA expression, levels of the calpastatin protein doublet were not increased, but rather slightly decreased under the hypoxic condition. Cardiac hypoxia was accompanied by preferential proteolytic cleavage of troponin I (TnI), one of the major myofibrillar proteins. Forced expression of calpastatin through an adenoviral vector effectively prevented the hypoxia- and calpain-mediated TnI proteolysis. Our results highlight the discordant expression pattern of cardiac calpastatin mRNA and protein in the hypoxic state. We suggest that although induction of calpastatin gene transcription may constitute a compensatory mechanism coping with the hypoxic stress, a sustained high calpastatin protein level appears to be essential in the intervention of the activated calpain proteolytic cascade.