LIPOSOMES: AN OVERVIEW

The discovery of liposome or lipid vesicle emerged from self forming enclosed lipid bi-layer upon hydration. Liposome drug delivery systems have played a significant role in formulation of potent drug to improve therapeutics. Recently the liposome formulations are targeted to reduce toxicity and increase accumulation at the target site. There are several new methods of liposome preparation based on lipid drug interaction and liposome disposition mechanism including the inhibition of rapid clearance of liposome by controlling particle size, charge and surface hydration. Most clinical applications of liposomal drug delivery are targeting to tissue with or without expression of target recognition molecules on lipid membrane. The liposomes are characterized with respect to physical, chemical and biological parameters. The sizing of liposome is also critical parameter which helps characterize the liposome which is usually performed by sequential extrusion at relatively low pressure through polycarbonate membrane (PCM). This mode of drug delivery lends more safety and efficacy to administration of several classes of drugs like antiviral, antifungal, antimicrobial, vaccines, anti tubercular drugs and gene therapeutics. Present applications of the liposomes are in the immunology, dermatology, vaccine adjuvant, eye disorders, brain targeting, infective disease and in tumour therapy. The new developments in this field are the specific binding properties of a drug-carrying liposome to a target cell such as a tumor cell and specific molecules in the body (antibodies, proteins, peptides etc.); stealth liposomes which are especially being used as carriers for hydrophilic (water soluble) anticancer drugs like doxorubicin, mitoxantrone; and bisphosphonate- liposome mediated depletion of macrophages. This review would be a help to the researchers working in the area of liposomal drug delivery

A fully coupled fluid-structure interaction model of the secondary lymphatic valve

The secondary lymphatic valve is a bi-leaflet structure frequent throughout collecting vessels that serves to prevent retrograde flow of lymph. Despite its vital function in lymph flow and apparent importance in disease development, the lymphatic valve and its associated fluid dynamics have been largely understudied. The goal of this work was to construct a physiologically relevant computational model of an idealized rat mesenteric lymphatic valve using fully coupled fluid-structure interactions to investigate the relationship between three-dimensional flow patterns and stress/deformation within the valve leaflets. The minimum valve resistance to flow, which has been shown to be an important parameter in effective lymphatic pumping, was computed as 268 g/mm4−s. Hysteretic behavior of the lymphatic valve was confirmed by comparing resistance values for a given transvalvular pressure drop during opening and closing. Furthermore, eddy structures were present within the sinus adjacent to the valve leaflets in what appear to be areas of vortical flow; the eddy structures were characterized by non-zero velocity values (up to ∼4 mm/s) in response to an applied unsteady transvalvular pressure. These modeling capabilities present a useful platform for investigating the complex interplay between soft tissue motion and fluid dynamics of lymphatic valves and contribute to the breadth of knowledge regarding the importance of biomechanics in lymphatic system function

Mechanism of pyruvate ferredoxin oxidoreductase and role of the (4Fe-4S) cluster of the corrinoid iron sulfur protein in acetyl COA synthesis by the Wood Ljungdahl pathway

Pyruvate ferredoxin oxidoreductase (PFOR) catalyzes the oxidative decarboxylation of pyruvate to acetyl CoA and CO\sb2. By using rapid freeze quench EPR and stopped-flow spectroscopy the three elementary steps that constitute the first reductive half reaction of the PFOR mechanism were elucidated. A hydroxyethyl-TPP radical was identified and characterized as a transient intermediate, and for the first time the kinetic competence of this substrate-derived radical was demonstrated. The CO\sb2 produced in the PFOR reaction was shown to be reduced to CO by CODH/ACS; subsequently, the CO generated binds in the ACS active site at a unique metal center to form a paramagnetic adduct the nickel iron carbon species. This bound carbonyl group then combines with a bound methyl group and coenzyme A to generate a third molecule of acetyl CoA. Two common intermediates were shown to be formed in acetyl CoA synthesis from CO\sb2: CO and the paramagnetic nickel iron carbon species making the Wood Ljungdahl pathway the first pathway in which CO is produced and then used as a metabolic intermediate. Both PFOR and CODH/ACS were also shown to be able to reduce protons to H\sb2 and at much lower rates, oxidize H\sb2 to protons and electrons. PFOR and CODH/ACS when incubated with their substrates/electron donors displayed self oxidation in the absence of an electron acceptor. The observed level of hydrogenase activity is physiologically relevant because it accounts for the rate of hydrogen production by growing cultures of Clostridium thermoaceticum. Another protein the corrinoid iron sulfur protein (CFeSP) which contains a cobalt ion housed in a corrinoid cofactor and an iron sulfur cluster catalyzes two key steps in the Wood Ljungdahl pathway. We have elucidated the role of the (4Fe-4S) cluster by site directed mutagenesis, and have demonstrated that it is required only in the reductive activation cycle that couples the oxidation of substrates like CO to the reduction of Co$\sp{+2}.

Construction of Concrete Verification Models from C++

C++ based verification methodologies are now emerging as the preferred method for SOC design. However most of the verification involving the C++ models are simulation based. The challenge of using C++ for sequential equivalence checking comes from two aspects (1) Language constructs such as pointers, polymorphism, virtual methods, dynamic memory allocation, dynamic loop bounds, floating points pose difficulty in creating a model suitable for equivalence checking (2) The memory and runtime required for creating models suitable for equivalence checking from practical C++ designs is huge. In this paper we describe techniques for constructing verification models from C++ designs containing a very rich set of language constructs. The flow is built keeping in mind that formal methods are inherently capacity constrained but need to be applied to large C++ designs to have practical value

Awareness, perceptions, and attitude towards Coronavirus disease 2019 vaccine among pregnant women in India: A cross-sectional study

Introduction: The present study was conducted to explore the awareness and perception of the coronavirus disease 2019 (COVID-19) vaccine among pregnant women. Material and Methods: A descriptive cross-sectional study was conducted from September 01, 2021, to September 28, 2021, among 301 pregnant women aged 18–35 years at antenatal care outpatient department in a tertiary care hospital of Western Maharashtra. Results: On assessing the knowledge and awareness score, the mean score (± standard deviation) was 7.83 ± 1.2 out of 16. A total of 176 (58.5%) had good scores (≥8). There was no statistically significant association between knowledge and awareness scores and the level of education, type of residence, and age or with weeks of gestation. Although the overall awareness of study participants was satisfactory, 177 (58.8%) felt that COVID-19 vaccines should be avoided during the first trimester. Interestingly, 45 (15.3%) felt that vaccines should not be given during menstruation. There were misconceptions about perceived contraindication, with 81(26.9%), 50(16.6%) and 43(14.4%) responding that diabetes, hypertension and heart disease are contradicts respectively. Interestingly, a total of 52 (17.3%) responded as likely when enquired whether the present vaccine can cause infertility. Similarly, about 62% of study participants felt that the vaccine might alter the DNA. Conclusion: The present study revealed good overall knowledge and awareness about the COVID-19 vaccine among pregnant with certain misconceptions. The findings suggest that immediate health education programs, risk communication, and correct information should be disseminated by respective health authorities

Inorganic polyphosphate accumulation suppresses the dormancy response and virulence in Mycobacterium tuberculosis

Stringent response pathways involving inorganic polyphosphate (PolyP) play an essential role in bacterial stress adaptation and virulence. The intracellular levels of PolyP are modulated by the activities of polyphosphate kinase-1 (PPK1), polyphosphate kinase-2 (PPK2), and exopolyphosphatases (PPXs). The genome of Mycobacterium tuberculosis encodes two functional PPXs, and simultaneous deletion of ppx1 and ppx2 results in a defect in biofilm formation. We demonstrate here that these PPXs cumulatively contribute to the ability of M. tuberculosis to survive in nutrient-limiting, low-oxygen growth conditions and also in macrophages. Characterization of single (Delta ppx2) and double knockout (dkppx) strains of M. tuberculosis indicated that PPX-mediated PolyP degradation is essential for establishing bacterial infection in guinea pigs. RNA-Seq-based transcriptional profiling revealed that relative to the parental strain, the expression levels of DosR regulon-regulated dormancy genes were significantly reduced in the dkppx mutant strain. In concordance, we also provide evidence that PolyP inhibits the autophosphorylation activities associated with DosT and DosS sensor kinases. The results in this study uncover that enzymes involved in PolyP homeostasis play a critical role in M. tuberculosis physiology and virulence and are attractive targets for developing more effective therapeutic interventions