Sustained release formulation of an anti-tuberculosis drug based on para-amino salicylic acid-zinc layered hydroxide nanocomposite

Background: Tuberculosis (TB), is caused by the bacteria, Mycobacterium tuberculosis and its a threat to humans since centuries. Depending on the type of TB, its treatment can last for 6-24 months which is a major cause for patients non-compliance and treatment failure. Many adverse effects are associated with the currently available TB medicines, and there has been no new anti-tuberculosis drug on the market for more than 50 year, as the drug development is very lengthy and budget consuming process.Development of the biocompatible nano drug delivery systems with the ability to minimize the side effects of the drugs, protection of the drug from enzymatic degradation. And most importantly the drug delivery systems which can deliver the drug at target site would increase the therapeutic efficacy. Nanovehicles with their tendency to release the drug in a sustained manner would result in the bioavalibilty of the drugs in the body for a longer period of time and this would reduce the dosing frequency in drug administration. The biocompatible nanovehicles with the properties like sustained release of drug of the target site, protection of the drug from physio-chemical degradation, reduction in dosing frequency, and prolong bioavailability of drug in the body would result in the shortening of the treatment duration. All of these factors would improve the patient compliance with chemotherapy of TB.Result: An anti-tuberculosis drug, 4-amino salicylic acid (4-ASA) was successfully intercalated into the interlamellae of zinc layered hydroxide (ZLH) via direct reaction with zinc oxide suspension. The X-ray diffraction patterns and FTIR analyses indicate that the molecule was successfully intercalated into the ZLH interlayer space with an average basal spacing of 24 Å. Furthermore, TGA and DTG results show that the drug 4-ASA is stabilized in the interlayers by electrostatic interaction. The release of 4-ASA from the nanocomposite was found to be in a sustained manner. The nanocomposite treated with normal 3T3 cells shows it reduces cell viability in a dose- and time-dependent manner.Conclusions: Sustained release formulation of the nanocomposite, 4-ASA intercalated into zinc layered hydroxides, with its ease of preparation, sustained release of the active and less-toxic to the cell is a step forward for a more patient-friendly chemotherapy of Tuberculosis

Negative incentive steering in a policy network

In this article the process of developing a policy for the recent comprehensive retrenchment operation in the Dutch university system is analysed from a theoretical point of view on decisionmaking. The article especially addresses the question whether some empirical evidence can be found for the rationalist view of collective decision-making, which states that a process of social communication should eventually lead to a unanimous and rational consensus concerning the selection of the optimal policy.\ud \ud The actual analysis concerns the way a retrenchment policy has been developed in a process of social communication between the most important actors: the Minister of Education and Science and the thirteen Dutch universities. It is assumed that the various communicative linkages between these actors can be interpreted as a policy network in which both governmental and non-governmental actors operate.\ud \ud The article concludes that in the Dutch university policy-network a complicated balance of interdependencies exists and that several sub-networks can be distinguished. It is also concluded that the Minister, while recognizing the interdependencies in the network, was able to use a special kind of (negative) incentive, inducing the universities to act as he wished.\ud \ud This negative incentive steering, however, also persuaded the universities to go to the utmost in their consultation efforts, thus trying to reach the rationalist ideal of collective decision-making. The final conclusion therefore is that the rationalist view of collective decision-making does not appear to be unrealistic. The article ends with a warning against a common mistake made regarding the normative appearance of the rationalist perspective

Systematic Identification of Combinatorial Drivers and Targets in Cancer Cell Lines

There is an urgent need to elicit and validate highly efficacious targets for combinatorial intervention from large scale ongoing molecular characterization efforts of tumors. We established an in silico bioinformatic platform in concert with a high throughput screening platform evaluating 37 novel targeted agents in 669 extensively characterized cancer cell lines reflecting the genomic and tissue-type diversity of human cancers, to systematically identify combinatorial biomarkers of response and co-actionable targets in cancer. Genomic biomarkers discovered in a 141 cell line training set were validated in an independent 359 cell line test set. We identified co-occurring and mutually exclusive genomic events that represent potential drivers and combinatorial targets in cancer. We demonstrate multiple cooperating genomic events that predict sensitivity to drug intervention independent of tumor lineage. The coupling of scalable in silico and biologic high throughput cancer cell line platforms for the identification of co-events in cancer delivers rational combinatorial targets for synthetic lethal approaches with a high potential to pre-empt the emergence of resistance

A randomized trial of multivitamin supplementation in children with tuberculosis in Tanzania

Children with tuberculosis often have underlying nutritional deficiencies. Multivitamin supplementation has been proposed as a means to enhance the health of these children; however, the efficacy of such an intervention has not been examined adequately. 255 children, aged six weeks to five years, with tuberculosis were randomized to receive either a daily multivitamin supplement or a placebo in the first eight weeks of anti-tuberculous therapy in Tanzania. This was only 64% of the proposed sample size as the trial had to be terminated prematurely due to funding constraints. They were followed up for the duration of supplementation through clinic and home visits to assess anthropometric indices and laboratory parameters, including hemoglobin and albumin. There was no significant effect of multivitamin supplementation on the primary endpoint of the trial: weight gain after eight weeks. However, significant differences in weight gain were observed among children aged six weeks to six months in subgroup analyses (n=22; 1.08 kg, compared to 0.46 kg in the placebo group; 95% CI=0.12, 1.10; p=0.01). Supplementation resulted in significant improvement in hemoglobin levels at the end of follow-up in children of all age groups; the median increase in children receiving multivitamins was 1.0 g/dL, compared to 0.4 g/dL in children receiving placebo (p<0.01). HIV-infected children between six months and three years of age had a significantly higher gain in height if they received multivitamins (n=48; 2 cm, compared to 1 cm in the placebo group; 95% CI=0.20, 1.70; p=0.01; p for interaction by age group=0.01). Multivitamin supplementation for a short duration of eight weeks improved the hematological profile of children with tuberculosis, though it didn't have any effect on weight gain, the primary outcome of the trial. Larger studies with a longer period of supplementation are needed to confirm these findings and assess the effect of multivitamins on clinical outcomes including treatment success and growth failure. CLINICALTRIALS.GOV IDENTIFIER: NCT00145184

DIPLOMACIA E POLÍTICA DOMÉSTICA: A LÓGICA DOS JOGOS DE DOIS NÍVEIS

A política doméstica e as relações internacionais com freqüência são inextricavelmente vinculadas; todavia,as teorias existentes (particularmente as estatocêntricas) não levam adequadamente em consideraçõestais vínculos. Quando os líderes nacionais devem obter as ratificações (formais ou informais) dos membrosde seus parlamentos para um acordo internacional, seus comportamentos em negociações refletem os imperativossimultâneos tanto de um jogo de política doméstica quanto de um jogo de política internacional.Usando exemplos de cúpulas econômicas ocidentais, das negociações do Canal do Panamá e do Tratado deVersalhes, dos programas de estabilização do Fundo Monetário Internacional, da Comunidade Européia ede muitos outros contextos diplomáticos, o artigo oferece uma teoria da ratificação. Ele enfatiza o papel daspreferências, coalizões, instituições e práticas domésticas, das estratégias e táticas dos negociadores, daincerteza, das reverberações domésticas das pressões externas e o papel dos interesses do negociador-chefe.Essa teoria de “jogos de dois níveis” também pode ser aplicável a muitos outros fenômenos políticos, taiscomo a dependência, os comitês legislativos e as coalizões multipartidárias