Current Issue : January - March Volume : 2013 Issue Number : 1 Articles : 6 Articles
Background and purpose of the study: Propylene glycol (PG) is a frequently co-administered solvent in formulations\r\nadministered to neonates, but reports on its (in)tolerance are limited. We aimed to report on renal, metabolic and\r\nhepatic tolerance before, during and following intravenous (iv) PG-paracetamol exposure and compared these data with\r\nsimilar datasets reported in literature on neonates exposed to PG without paracetamol or paracetamol without PG.\r\nMethods: Renal (diuresis, creatinemia, sodium), metabolic (Base Excess, Anion Gap, lactate, bicarbonate) and hepatic\r\n(liver enzymes, bilirubinemia) indicators before, during and following iv paracetamol-PG exposure in neonates as\r\nincluded in the PARANEO (paracetamol in neonates) study (intra-individual trends, ANOVA) were collected and analysed.\r\nComparison with observations collected in cases exposed to either iv phenobarbital-PG or iv paracetamol-mannitol\r\n(inter-individual comparison, Mann Whitney-U test) were made.\r\nResults: PG exposure (median 34.1 mg/kg/24 h) did not affect postnatal renal, metabolic and hepatic adaptations in 60\r\ncases exposed to paracetamol-PG. These indicators were similar when compared to 29 cases exposed to phenobarbital-\r\nPG or 172 cases exposed to paracetamol-mannitol.\r\nMajor conclusion: Based on observations in 89 neonates, low dose PG exposure was tolerated well. Studies on PG\r\npharmacokinetics and its covariates are needed to estimate the upper level of PG tolerance in neonates....
Magnolia officinalis has been widely used in traditional Chinese medicine. Magnolol, an active component isolated\r\nfrom Magnolia officinalis, is known to be a cardiovascular protector since 1994. The multiplex mechanisms of\r\nmagnolol on cardiovascular protection depends on cell types and dosages, and will be reviewed and discussed in\r\nthis article. Magnolol under low and moderate dosage possesses the ability to protect heart from ischemic/\r\nreperfusion injury, reduces atherosclerotic change, protects endothelial cell against apoptosis and inhibits\r\nneutrophil-endothelial adhesion. The moderate to high concentration of magnolol mainly acts on smooth muscle\r\ncells and platelets. Magnolol induces apoptosis in vascular smooth muscle cells at moderate concentration and\r\ninhibits proliferation at moderate and high concentration. High concentration of magnolol also abrogates platelet\r\nactivation, aggregation and thrombus formation. Magnolol also serves as an smooth muscle relaxant only upon the\r\nhigh concentration. Oral intake of magnolol to reach the therapeutic level for cardiovascular protection is\r\napplicable, thus makes magnolol an agent of great potential for preventing cardiovascular diseases in high-risk\r\npatients....
Background: The growing use of imaging procedures in medicine has raised concerns about exposure to lowdose\r\nionising radiation (LDIR). While the disastrous effects of high dose ionising radiation (HDIR) is well\r\ndocumented, the detrimental effects of LDIR is not well understood and has been a topic of much debate. Since\r\nlittle is known about the effects of LDIR, various kinds of wet-lab and computational analyses are required to\r\nadvance knowledge in this domain. In this paper we carry out an ââ?¬Å?upside-down pyramidââ?¬Â form of systems biology\r\nanalysis of microarray data. We characterised the global genomic response following 10 cGy (low dose) and\r\n100 cGy (high dose) doses of X-ray ionising radiation at four time points by analysing the topology of gene\r\ncoexpression networks. This study includes a rich experimental design and state-of-the-art computational systems\r\nbiology methods of analysis to study the differences in the transcriptional response of skin cells exposed to low\r\nand high doses of radiation.\r\nResults: Using this method we found important genes that have been linked to immune response, cell survival\r\nand apoptosis. Furthermore, we also were able to identify genes such as BRCA1, ABCA1, TNFRSF1B, MLLT11 that\r\nhave been associated with various types of cancers. We were also able to detect many genes known to be\r\nassociated with various medical conditions.\r\nConclusions: Our method of applying network topological differences can aid in identifying the differences among\r\nsimilar (eg: radiation effect) yet very different biological conditions (eg: different dose and time) to generate\r\ntestable hypotheses. This is the first study where a network level analysis was performed across two different\r\nradiation doses at various time points, thereby illustrating changes in the cellular response over time....
The purpose of this research was to study mucoadhesive bilayer tablets of Cefuroxime Axetil (CA) using the mucoadhesive polymers HPMC and Carbopol 934P along with ethyl cellulose as an impermeable nonmucoadhesive backing layer. CA incorporated in the adhesive layer of the tablet, which comes in contact with the mucosal surface of intestine. In addition to achieve unidirectional release toward the mucosa, ethyl cellulose used as a backing layer. Eudragit L100 was used as enteric coating material. Eudragit L100 coated tablet release the drug only at higher pH. Response surface designs were adequately applied to study the effect of different formulation variables on the release profile and mucoadhesive strength to select optimized formulation. Results indicate that release profile and mucoadhesion properties of tablets can be controlled by changing the polymer type and concentration....
Background: We aimed to assess whether high-dose preoperative chemoradiotherapy (CRT) improves outcome in\r\nesophageal cancer patients compared to surgery alone and to define possible prognostic factors for overall survival.\r\nMethods: Hundred-and-seven patients with disease stage IIA - III were treated with either surgery alone (n = 45) or\r\nhigh-dose preoperative CRT (n = 62). The data were collected retrospectively. Sixty-seven patients had\r\nadenocarcinomas, 39 squamous cell carcinomas and one undifferentiated carcinoma. CRT was given as three intensive\r\nchemotherapy courses by cisplatin 100 mg/m2 on day 1 and 5-fluorouracil 1000 mg/m2/day, from day 1 through day 5\r\nas continuous infusion. One course was given every 21 days. The last two courses were given concurrent with highdose\r\nradiotherapy, 2 Gy/fraction and a median dose of 66 Gy. Kaplan-Meier survival analysis with log rank test was used\r\nto obtain survival data and Cox Regression multivariate analysis was used to define prognostic factors for overall\r\nsurvival.\r\nResults: Toxicity grade 3 of CRT occurred in 30 (48.4%) patients and grade 4 in 24 (38.7%) patients of 62 patients. One\r\npatient died of neutropenic infection (grade 5). Fifty percent (31 patients) in the CRT group did undergo the planned\r\nsurgery. Postoperative mortality rate was 9% and 10% in the surgery alone and CRT+ surgery groups, respectively (p =\r\n1.0). Median overall survival was 11.1 and 31.4 months in the surgery alone and CRT+ surgery groups, respectively (log\r\nrank test, p = 0.042). In the surgery alone group one, 3 and 5 year survival rates were 44%, 24% and 16%, respectively\r\nand in the CRT+ surgery group they were 68%, 44% and 29%, respectively. By multivariate analysis we found that age of\r\npatient, performance status, alcoholism and > = 4 pathological positive lymph nodes in resected specimen were\r\nsignificantly associated with overall survival, whereas high-dose preoperative CRT was not.\r\nConclusion: We found no significant survival advantage in esophageal cancer stage IIA-III following preoperative highdose\r\nCRT compared to surgery alone. Patient''s age, performance status, alcohol abuse and number of positive lymph\r\nnodes were prognostic factors for overall survival....
Drug development is tedious, cost-effective and complex process. Microdosing uses less than 1/100th of the dose calculated to yield a pharmacological effect of the test substance to a maximum dose of <100 micrograms. It helps in early pharmacokinetic evaluation of new drug molecules, which helps in the early selection of promising compounds. Unsuitable molecules can be eliminated earlier which reduces costs and avoids the unnecessary exposure of subjects in the trial to non-viable. The risk of human toxicity is less because of short duration administration. Regulatory requirements for microdosing trials are flexible and limited, which is an advantage compared to phase I. Microdosing may help both patients and the pharmaceutical industry with earlier availability of new test drugs, reduced failure of compounds at later stages and reduce the cost of drug development. This review clearly describes the role of microdosing in drug development process....
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