Remodeling of Fibrous Extracellular Matrices by Contractile Cells: Predictions from Discrete Fiber Network Simulations

Contractile forces exerted on the surrounding extracellular matrix (ECM) lead to the alignment and stretching of constituent fibers within the vicinity of cells. As a consequence, the matrix reorganizes to form thick bundles of aligned fibers that enable force transmission over distances larger than the size of the cells. Contractile force-mediated remodeling of ECM fibers has bearing on a number of physiologic and pathophysiologic phenomena. In this work, we present a computational model to capture cell-mediated remodeling within fibrous matrices using finite element based discrete fiber network simulations. The model is shown to accurately capture collagen alignment, heterogeneous deformations, and long-range force transmission observed experimentally. The zone of mechanical influence surrounding a single contractile cell and the interaction between two cells are predicted from the strain-induced alignment of fibers. Through parametric studies, the effect of cell contractility and cell shape anisotropy on matrix remodeling and force transmission are quantified and summarized in a phase diagram. For highly contractile and elongated cells, we find a sensing distance that is ten times the cell size, in agreement with experimental observations.Comment: Accepted for publication in the Biophysical Journa

Changing Profile of Leprosy in a Tertiary Care Hospital

WHO (World Health Organization) has fixed the target of zero grade 2 (G2D) deformity among pediatric leprosy patients and reduction of new leprosy cases with G2D to less than one case per million population, to be achieved by 2020. It has also mentioned the performing indicators to evaluate the progress of leprosy control program. We undertook this study to find out what changes the leprosy clinic at our hospital had witnessed in terms of the WHO performance indicators and whether we had progressed toward reaching the goal fixed by WHO. The important indicators such as number of new cases, percentage of MB cases, child cases, and G2D cases were examined from the year 2012-13 to 2016-17. Although a significant reduction in G2D cases, MB cases and child cases were noted, which is quite encouraging, yet the numbers of annual new cases detected remained almost static during the study period, indicating persistence of active transmission of infection and the need for augmented active surveillance (leprosy case detection campaign), contact tracing, community awareness, stigma reduction and training

Emerging technologies for the non-invasive characterization of physical-mechanical properties of tablets

The density, porosity, breaking force, viscoelastic properties, and the presence or absence of any structural defects or irregularities are important physical-mechanical quality attributes of popular solid dosage forms like tablets. The irregularities associated with these attributes may influence the drug product functionality. Thus, an accurate and efficient characterization of these properties is critical for successful development and manufacturing of a robust tablets. These properties are mainly analyzed and monitored with traditional pharmacopeial and non-pharmacopeial methods. Such methods are associated with several challenges such as lack of spatial resolution, efficiency, or sample-sparing attributes. Recent advances in technology, design, instrumentation, and software have led to the emergence of newer techniques for non-invasive characterization of physical-mechanical properties of tablets. These techniques include near infrared spectroscopy, Raman spectroscopy, X-ray microtomography, nuclear magnetic resonance (NMR) imaging, terahertz pulsed imaging, laser-induced breakdown spectroscopy, and various acoustic- and thermal-based techniques. Such state-of-the-art techniques are currently applied at various stages of development and manufacturing of tablets at industrial scale. Each technique has specific advantages or challenges with respect to operational efficiency and cost, compared to traditional analytical methods. Currently, most of these techniques are used as secondary analytical tools to support the traditional methods in characterizing or monitoring tablet quality attributes. Therefore, further development in the instrumentation and software, and studies on the applications are necessary for their adoption in routine analysis and monitoring of tablet physical-mechanical properties

Physical properties and solubility studies of Nifedipine-PEG 1450/HPMCAS-HF solid dispersions

Low-order high-energy nifedipine (NIF) solid dispersions (SDs) were generated by melt solvent amorphization with polyethylene glycol (PEG) 1450 and hypromellose acetate succinate (HPMCAS-HF) to increase NIF solubility while achieving acceptable physical stability. HPMCAS-HF was used as a crystallization inhibitor. Individual formulation components, their physical mixtures (PMs), and SDs were characterized by differential scanning calorimetry, powder X-ray diffraction, and Fourier transform infrared spectroscopy (FTIR). NIF solubility and percent crystallinity (PC) were determined at the initial time and after 5 days stored at 25 °C and 60% RH. FTIR indicated that hydrogen bonding was involved with the amorphization process. FTIR showed that NIF:HPMCAS-HF intermolecular interactions were weaker than NIF:PEG 1450 interactions. NIF:PEG 1450 SD solubilities were significantly higher than their PM counterparts (p \u3c 0.0001). The solubilities of NIF:PEG 1450:HPMCAS-HF SDs were significantly higher than their corresponding NIF:PEG 1450 SDs (p \u3c 0.0001-0.043). All the SD solubilities showed a statistically significant decrease (p \u3c 0.0001) after storage for 5 days. SDs PC were statistically lower than their comparable PMs (p \u3c 0.0001). The PCs of SDs with HPMCAS-HF were significantly lower than SDs not containing only PEG 1450. All SDs exhibited a significant increase in PC (p \u3c 0.0001–0.0089) on storage. Thermogravimetric analysis results showed that HPMCAS-HF bound water at higher temperatures than PEG 1450 (p \u3c 0.0001–0.0039). HPMCAS-HF slowed the crystallization process of SDs, although it did not completely inhibit NIF crystal growth