Impact of tuberculosis treatment on health-related quality of life of pulmonary tuberculosis patients: a follow-up study.

BACKGROUND: At present, much of the attention within tuberculosis (TB) management is spent on microbiological cure, and its impact on health-related quality of life (HRQoL) is either undervalued or seldom considered. The aim of this study was to evaluate the impact of TB treatment on HRQoL of new smear positive pulmonary tuberculosis (PTB) patients. Moreover, we also aimed to determine whether the selected socio-demographic and clinical variables were predictive of variability in the HRQoL scores over time. METHODS: This was a prospective follow-up of new smear positive PTB patients who were diagnosed at the chest clinic of Penang General Hospital between March 2010 and February 2011. All eligible patients (i.e., a new case of smear positive PTB, literate and aged 18 years or above) were asked to self-complete the SF-36v2 questionnaire at the start of their treatment, and then subsequently after the intensive phase and at the end of the treatment. A score on a health domain or component summary measure that was less than 47 norm-based scoring (NBS) point was considered indicative of impaired function within that health domain or dimension. Likewise, an individual having mental component summary (MCS) score ≤ 42 NBS point was considered to be at the risk of depression. Repeated measures ANOVA test was performed to examine how the summary scores varied over time, and to determine whether independent variables were predictive of variability in the physical component summary (PCS) and MCS scores over time. RESULTS: A total of 216 patients completed the SF-36v2 questionnaire at the start of their treatment. Out of these, 177 and 153 completed the questionnaire at the second and third follow-ups, respectively. The mean PCS scores at the start of the treatment, after the intensive phase and at the end of treatment were 41.9 (SD 5.1), 45.8 (SD 4.8) and 46.0 (SD 6.9), respectively. Similarly, the mean MCS scores at the start of the treatment, after the intensive phase and at the end of the treatment were 39.9 (SD 7.3), 45.0 (SD 6.8) and 46.8 (SD 7.8), respectively. More than 23% of the patients were at the risk of depression at the end of their TB treatment. Patient's age and being a smoker were predictive of differences in the PCS scores. Similarly, monthly income, being a smoker and TB-related symptoms at the start of the treatment were predictive of differences in the MCS scores. CONCLUSION: Although HRQoL improved with the treatment, the scores on component summary measures showed compromised physical and mental health among study patients even at the end of their TB treatment.

Naproxen release from sustained release matrix system and effect of cellulose derivatives.

The present study was conducted to investigate the low viscosity grades of hydroxypropylmethyl cellulose (HPMC) and ethyl cellulose (EC) in sustaining the release of water insoluble drug, naproxen from the matrix tablets. Both HPMC and EC were incorporated in the matrix system separately or in combinations by wet granulation technique. In vitro dissolution studies indicated that EC significantly reduced the rate of drug release compared to HPMC in 12 hour testing time. But, no significant difference was observed in the release profiles of matrix tablets made by higher percentages of EC. The tablets prepared with various combinations of HPMC and EC also failed to produce produce the desired release profiles. However, comparatively linear and desirable sustained release was obtained from EC-based matrix tablets prepared by slightly modifying the granulation method. Moreover, two different compression forces used in tableting had no remarkable effect on the release profile of naproxen.

Hyaluronic Acid-Tocopherol Succinate-Based Self-Assembling Micelles for Targeted Delivery of Rifampicin to Alveolar Macrophages.

We developed a target drug delivery system for the treatment of tuberculosis using rifampicin (RIF) incorporated into hyaluronic acid-tocopherol succinate (HA-TS) micelles. The RIF-HA-TS micelles were physicochemically characterized and the cellular uptake of RIF-HA-TS micelles on murine alveolar macrophage MH-S cells was investigated. Furthermore, the cytokine secreting activities of the alveolar macrophages after treatment with RIF-HA-TS micelles were evaluated. The results of the studies indicate that (i) mean particle size of HA-TS micelles was in the range of 212-294.6 nm depending on the degree of substitution (DS) of the hydrophobic moiety. The incorporated RIF was sustained released from RIF loaded HA-TS micelles (ii) cellular uptake of RIF-HA-TS micelles was dose and energy dependent (iii) RIF-HA-TS micelles had a significant uptake in comparison to free RIF, with the highest uptake at 12 h (iv) RIF-HA-TS micelles were taken up into cells via phygocytosis as well as CD44 receptor-mediate endocytosis (v) beside E. coli lipopolysccharide (LPS), HA-TS micelles also could activate MH-S cells, which improved the RIF-HA-TS uptake (vi) RIF-HA-TS micelles induced higher concentration of Th1 cytokines than free drug, which will help to enhance the anti-tuberculosis activity. The results of the current studies demonstrate the feasibility of targeting macrophages and the possibility of using the HA-TS micelles for tuberculosis treatment.

Sonic hedgehog signalling pathway: a complex network.

Sonic Hedgehog (Shh) signalling cascade is one of the intricate signal transduction mechanisms that govern the precisely regulated developmental processes of multicellular organisms. Along with establishing the patterns of cellular differentiation to direct complex organ formation, it also has an important role in post-embryonic tissue regeneration and repair processes. Especially, Shh signalling is implicated in the induction of multifarious neuronal populations in central nervous system. There is compelling evidence of the involvement of Shh protein in the signalling network that regulates various morphogenetic processes such as the exquisite neural tube pattern formation. In the morphogenetic field, the activation of Shh signalling processes is intricately linked to the alterations at the molecular level in the structure of Shh protein that leads to its altered biophysical and biochemical reactivity. This brief article gives an overview of such complex cascade of events in Shh signalling and its transduction pathways.

Microcalorimetric method to assess phagocytosis: macrophage-nanoparticle interactions.

This study evaluated the use of isothermal microcalorimetry (ITMC) to detect macrophage-nanoparticle interactions. Four different nanoparticle (NP) formulations were prepared: uncoated poly(isobutyl cyanoacrylate) (PIBCA), polysorbate-80-coated PIBCA, gelatin, and mannosylated gelatin NPs. Changes in NP formulations were aimed to either enhance or decrease macrophage-NP interactions via phagocytosis. Alveolar macrophages were cultured on glass slabs and inserted in the ITMC instrument. Thermal activities of the macrophages alone and after titration of 100 µL of NP suspensions were compared. The relative interactive coefficients of macrophage-NP interactions were calculated using the heat exchange observed after NP titration. Control experiments were performed using cytochalasin B (Cyto B), a known phagocytosis inhibitor. The results of NP titration showed that the total thermal activity produced by macrophages changed according to the NP formulation. Mannosylated gelatin NPs were associated with the highest heat exchange, 75.4 ± 7.5 J, and thus the highest relative interactive coefficient, 9,269 ± 630 M-1. Polysorbate-80-coated NPs were associated with the lowest heat exchange, 15.2 ± 3.4 J, and the lowest interactive coefficient, 890 ± 120 M-1. Cyto B inhibited macrophage response to NPs, indicating a connection between the thermal activity recorded and NP phagocytosis. These results are in agreement with flow cytometry results. ITMC is a valuable tool to monitor the biological responses to nano-sized dosage forms such as NPs. Since the thermal activity of macrophage-NP interactions differed according to the type of NPs used, ITMC may provide a method to better understand phagocytosis and further the development of colloidal dosage forms.

Pulmonary delivery of inhalable nanoparticles: dry powder inhalers.

Pulmonary administration of inhalable nanoparticles (NPs) is an emerging area of interest. Dry powder inhalers may offer particular advantages for pulmonary administration of NPs. This article reviews research performed on the formulation of inhalable NPs as dry powder to achieve deep-lung deposition and enhance NP redispersibility. Moreover, the article summarizes up-to-date in vivo applications of inhalable NPs as dry powder inhalers.

Ethyl cellulose-based solid matrix system for sustaining release of naproxen.

The present study was conducted to develop sustained release matrix tablets of naproxen with the help of a hydrophobic polymer, Ethyl Cellulose (EC). Matrix tablets were prepared by incorporating various proportions of EC in the matrix system using wet granulation technique. The rate of drug release from the matrix tablets was found to be very slow and could not produce the desired release profiles in 12 h testing time. However, the tablets prepared by slightly modifying the wet granulation method exhibited comparatively linear and desirable release rate. No significant difference in the release profiles of naproxen matrix tablets was observed at different stirring speeds and storage conditions.