Optimization of Drug Delivery Systems for Intraperitoneal Therapy to Extend the Residence Time of the Chemotherapeutic Agent.
Optimization of drug delivery systems for intraperitoneal therapy to extend the residence time of the chemotherapeutic agent.
ScientificWorldJournal. 2013; 2013: 720858
De Smet L, Ceelen W, Remon JP, Vervaet C
Intraperitoneal (IP) chemotherapy is an effective way of treating peritoneal carcinomatosis of colorectal origin after complete cytoreduction. Although IP therapy has been already performed for many years, no standardized treatment design has been developed in terms of schedule, residence time, drug, or carrier solution. Because of the fast clearance of the conventional intravenous (IV) drug delivery systems used for IP therapy, a lot of research is performed to optimize IP drug delivery and extend the residence time of the cytotoxic agent in the peritoneal cavity. This paper reviews the recent advances made in drug delivery systems for IP chemotherapy, discussing the use of microparticles, nanoparticles, liposomes, micelles, implants, and injectable depots for IP delivery. HubMed – drug
Prevalence of drug resistance and culture-positive rate among microorganisms isolated from patients with ocular infections over a 4-year period.
Clin Ophthalmol. 2013; 7: 695-702
Shimizu Y, Toshida H, Honda R, Matsui A, Ohta T, Asada Y, Murakami A
To investigate the microbial isolates from patients with ocular infections and the trend in the emergence of levofloxacin-resistant strains over the past four years from 2006 to 2009 retrospectively.The subjects were 242 patients with ocular infections or traumas treated in our hospital including outpatients, inpatients, and emergency room patients. Most of them needed urgent care presenting with eye complaints, traumas, or decreased vision. Clinical samples were obtained from discharges, corneal, conjunctival tissues or vitreous fluid or aqueous humor, and cultured. Items for assessment included the patient’s age, the diagnosis, the prevalence of isolated bacteria, and the results of susceptibility tests for levofloxacin (LVFX) cefamezin (CEZ), gentamicin (GM) and vancomycin. This information was obtained from the patients’ medical records.There were 156 male patients and 86 female patients who were aged from 2 months old to 94 years old and mean age was 56.8 ± 24.2 years. Of the 242 patients, 78 (32.2%) had positive cultures. The culture-positive rate was significantly higher in male patients than female in total (P = 0.002) and in patients with corneal perforation (P = 0.005). Corneal perforation was the highest culture-positive rate (60.0%), followed by orbital cellulitis (56.5%), blepharitis (50.0%), dacryoadenitis (45.5%), conjunctivitis (38.2%), infectious corneal ulcer (28.5%) and endophthalmitis (24.7%). LVFX-resistant strains accounted for 40 out of a total of 122 strains (32.8%), and the minimum inhibitory concentration (MIC) was significantly higher in LVFX and GM compared with the other antibiotics. There were no vancomycin-resistant strains.Attention should be paid to a possible future increase of strains with resistance to LVFX, as commonly prescribed ocular antibiotics bring emergence of resistant bacteria. Although no vancomycin-resistant strains were isolated this drug should be reserved as the last resort, in order to prevent the emergence of vancomycin resistance. HubMed – drug
The food dye FD&C Blue No. 1 is a selective inhibitor of the ATP release channel Panx1.
J Gen Physiol. 2013 Apr 15;
Wang J, Jackson DG, Dahl G
The food dye FD&C Blue No. 1 (Brilliant Blue FCF [BB FCF]) is structurally similar to the purinergic receptor antagonist Brilliant Blue G (BBG), which is a well-known inhibitor of the ionotropic P2X7 receptor (P2X7R). The P2X7R functionally interacts with the membrane channel protein pannexin 1 (Panx1) in inflammasome signaling. Intriguingly, ligands to the P2X7R, regardless of whether they are acting as agonists or antagonists at the receptor, inhibit Panx1 channels. Thus, because both P2X7R and Panx1 are inhibited by BBG, the diagnostic value of the drug is limited. Here, we show that the food dye BB FCF is a selective inhibitor of Panx1 channels, with an IC50 of 0.27 µM. No significant effect was observed with concentrations as high as 100 µM of BB FCF on P2X7R. Differing by just one hydroxyl group from BB FCF, the food dye FD&C Green No. 3 exhibited similar selective inhibition of Panx1 channels. A reverse selectivity was observed for the P2X7R antagonist, oxidized ATP, which in contrast to other P2X7R antagonists had no significant inhibitory effect on Panx1 channels.Based on its selective action, BB FCF can be added to the repertoire of drugs to study the physiology of Panx1 channels. Furthermore, because Panx1 channels appear to be involved directly or indirectly through P2X7Rs in several disorders, BB FCF and derivatives of this “safe” food dye should be given serious consideration for pharmacological intervention of conditions such as acute Crohn’s disease, stroke, and injuries to the central nervous system. HubMed – drug
Enhanced Vasodilator Activity of Nitrite in Hypertension: Critical Role for Erythrocytic Xanthine Oxidoreductase and Translational Potential.
Hypertension. 2013 Apr 15;
Ghosh SM, Kapil V, Fuentes-Calvo I, Bubb KJ, Pearl V, Milsom AB, Khambata R, Maleki-Toyserkani S, Yousuf M, Benjamin N, Webb AJ, Caulfield MJ, Hobbs AJ, Ahluwalia A
Elevation of circulating nitrite (NO2(-)) levels causes vasodilatation and lowers blood pressure in healthy volunteers. Whether these effects and the underpinning mechanisms persist in hypertension is unknown. Therefore, we investigated the consequences of systemic nitrite elevation in spontaneously hypertensive rats and conducted proof-of-principle studies in patients. Nitrite caused dose-dependent blood pressure-lowering that was profoundly enhanced in spontaneously hypertensive rats versus normotensive Wistar Kyoto controls. This effect was virtually abolished by the xanthine oxidoreductase (XOR) inhibitor, allopurinol, and associated with hypertension-specific XOR-dependent nitrite reductase activity localized to the erythrocyte but not the blood vessel wall. To determine whether these pathways translate to human hypertension, we investigated the effects of elevation of circulating nitrite levels in 15 drug naïve grade 1 hypertensives. To elevate nitrite, we used a dose of dietary nitrate (?3.5 mmol) that elevated nitrite levels ?1.5-fold (P<0.01); a rise shown previously to exert no significant blood pressure-lowering effects in normotensives. This dose caused substantial reductions in systolic (?12 mm Hg) and diastolic blood pressures (P<0.001) and pulse wave velocity (P<0.05); effects associated with elevations in erythrocytic XOR expression and XOR-dependent nitrite reductase activity. Our observations demonstrate the improved efficacy of inorganic nitrate and nitrite in hypertension as a consequence of increased erythrocytic XOR nitrite reductase activity and support the concept of dietary nitrate supplementation as an effective, but simple and inexpensive, antihypertensive strategy. HubMed – drug