Doxorubicin-loaded phosphatidylethanolamine-conjugated nanoliposomes: in vitro characterization and their accumulation in liver, kidneys, and lungs in rats

Anandamoy Rudra, R Manasa Deepa, Miltu Kumar Ghosh, Subhajit Ghosh, Biswajit MukherjeeDepartment of Pharmaceutical Technology, Jadavpur University, Kolkata (Calcutta), IndiaIntroduction: Phosphatidylethanolamine (PE)-conjugated nanoliposomes were developed, characterized, and investigated for their accumulation in liver, kidneys, and lungs in rats.Methods: Drug-excipient interaction was studied using Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), surface morphology by field emission scanning electron microscopy, elemental analysis by energy dispersive X-ray (EDX) analysis, zeta potential and size distribution using a Zetasizer and particle size analyzer, and in vitro drug release by dialysis membrane. In vivo accumulation of liposomes in tissues was also studied.Results: No chemical reaction was observed between drug and excipients. EDX study confirmed PE-conjugation in liposomes. Doxorubicin-loaded liposomes (DOX-L) and PE-conjugated doxorubicin-loaded liposomes (DOX-PEL) were of smooth surface and homogenously distributed in nanosize range (32–37 nm) with a negative surface charge. Loading efficiencies were 49.25% ± 1.05% and 52.98% ± 3.22% respectively, for DOX-L and DOX-PEL. In vitro drug release study showed 69.91% ± 1.05% and 77.07% ± 1.02% doxorubicin released, from DOX-L and DOX-PEL, respectively, in nine hours. Fluorescence microscopic study showed that liposomes were well distributed in liver, lungs, and kidneys.Conclusion: Data suggests that PE-conjugated nanoliposomes released the drug in a sustained manner and were capable of distributing them in various organs. This may be used for cell/ tissue targeting, attaching specific antibodies to PE.Keywords: doxorubicin, phosphatidylethanolamine-conjugated nanoliposomes, tissue accumulatio

Student understanding of the direction of force due to atmospheric pressure: A tale of two models

The direction of force due to atmospheric pressure is a difficult idea for students to understand. We report a study, involving 35 middle school students, which points towards the existence of two contrasting mental models of atmospheric pressure(Patm), which we term the Weight Model (WM) and the Collision Model (CM). Our analysis reveals a predisposition among students to adhere to the WM, wherein they consider Patm akin to a column of air pressing down on the surface of the earth (Tytler,1998). In our presentation, we discuss everyday experiences and textbook presentations as two plausible sources for this predisposition. Our study involves the analysis of the student discourse as they participated in an activity to estimate the value of atmospheric pressure using a syringe and some easily available materials (Inversin, 1977). Students worked in small groups of 3 to 4, facilitated by instructors. Our goal was to help students engage in discussion, wherein they explicitly articulated their ideas and considered notions from others in an authentic context, thereby paving the way for a revision of their own ideas. The activity had the following components: a) A pre-activity questionnaire: A set of 6 questions, aimed at eliciting students’ prior conceptions and basic understanding related to atmospheric pressure. These written responses subsequently served as the basis for discussion among students, within and across student groups. b) A demonstration to show the action of atmospheric pressure: Instructors illustrated the action of atmospheric pressure on the syringe and its directionality. The demonstration sought to scaffold students’ thinking while engaging with the difficult notion of the direction of force due to atmospheric pressure. c) Activity to estimate the magnitude of atmospheric pressure: In this part the students have to design an experiment using the syringe to calculate the value of atmospheric pressure. The experimental design involves a balancing condition between 3 forces: static friction between the barrel and piston of the syringe, force due to atmospheric pressure and weight hung on the syringe. d) Post activity questionnaire: The final part of the activity is a set of questions aimed at checking whether there was any change in student response patterns pertaining to atmospheric pressure. Our analysis reveals that the activity and associated discussions show potential to facilitate students’ transition from the WM to the CM. We present evidence of modest conceptual gains characterized by micro-transitions in students’ problem-solving strategies, being increasingly inclined towards the canonical CM rather than the intuitive WM of the atmosphere. We also present some problematic discourse patterns, which are likely widespread in traditional lecture-based Physics classrooms. REFERENCES Inversin, A. R. (1977). Measuring Atmospheric Pressure with a Syringe. Physics Teacher, 15(4), 232-233. Tytler, R. (1998). Children’s conceptions of air pressure: Exploring the nature of conceptual change. International Journal of Science Education, 20(8), 929–958. https://doi.org/10.1080/095006998020080

A novel 1,1’-bis-[2-(1H-indole-3-yl)-ethyl]-4,4′-bipyridinium diperchlorate (viologen) for a high contrast electrochromic device

A new organic electrochromic material, 1,1’-bis-[2-(1H-indole-3-yl)-ethyl]-4,4′-bipyridinium diperchlorate (viologen) was synthesized by di-quaternization of 4,4′-bipyridyl using 3-(2-bromoethyl)-indole under the assistance of microwave irradiation with high yields and in short reaction times. The compound (IEV) was characterized by 1H-NMR, 13C-NMR and FTIR spectroscopic methods. Thermal decomposition temperature of indole viologen perchlorate is above 3000C. An electrochromic device, containing IEV salt in N,N-Dimethylformamide (DMF) and 1-ethyl-3-methylimidazolium bis-(trifluoromethylsulfonyl)-imide (ionic liquid) as electrolyte was constructed, where Prussian blue was used as counter electrode. IEV is a cathodically coloring organic electrochromic material and thus the device underwent reversible transitions between transparent and deep blue hues; the color change was accompanied by an excellent optical contrast (57% at 605 nm), a large coloration efficiency of 533 cm2 C-1 at 605 nm and switching times of 2 s. The device was subjected to repetitive switching between the colored and bleached states and was found that almost no loss in redox activity up to 2000 cycles, ratifying its suitability for electrochromic window/display applications

Y chromosome deletions in azoospermic men in India

Genetic factors cause about 10% of male infertility. Azoospermia factors (AZFa, AZFb, AZFc) are considered to be the most important for spermatogenesis. We therefore made an attempt to evaluate the genetic cause of azoospermia, Y chromosome deletion in particular, in Indian men. We have analyzed a total of 570 men, including 340 azoospermic men and 230 normal control subjects. DNA samples were initially screened with 30 sequence-tagged site (STS) markers representing AZF regions (AZFa, AZFb, AZFc). Samples, with deletion in the above regions were mapped by STS walking. Further, the deletions were confirmed by Southern hybridization using the probes from both euchromatic and heterochromatic regions. Of the total 340 azoospermic men analyzed, 29 individuals (8.5%) showed Y chromosome deletion, of which deletion in AZFc region was the most common (82.8%) followed by AZFb (55.2%) and AZFa (24.1%). Microdeletions were observed in AZFa, whereas macrodeletions were observed in AZFb and AZFc regions. Deletion of heterochromatic and azoospermic regions was detected in 20.7% of the azoospermic men. In 7 azoospermic men, deletion was found in more than 8.0 Mb spanning AZFb and AZFc regions. Sequence analysis at the break points on the Y chromosome revealed the presence of L1, ERV, and other retroviral repeat elements. We also identified a 240-kb region consisting of 125 bp tandem repeats predominantly comprised of ERV elements in the AZFb region. Histological study of the testicular tissue of the azoospermic men, who showed Y chromosome deletion, revealed complete absence of germ cells and presence of only Sertoli cells

Prevalence and incidence of hypertension: Results from a representative cohort of over 16,000 adults in three cities of south Asia

Background: Despite high projected burden, hypertension incidence data are lacking in South Asian population. We measured hypertension prevalence and incidence in the Center for cArdio-metabolic Risk Reduction in South Asia (CARRS) adult cohort.Methods: The CARRS Study recruited representative samples of Chennai, Delhi, and Karachi in 2010/11, and socio-demographic and risk factor data were obtained using a standard common protocol. Blood pressure (BP) was measured in the sitting position using electronic sphygmomanometer both at baseline and two year follow-up. Hypertension and control were defined by JNC 7 criteria.Results: In total, 16,287 participants were recruited (response rate=94.3%) and two year follow-up was completed in 12,504 (follow-up rate=79.2%). Hypertension was present in 30.1% men (95% CI: 28.7-31.5) and 26.8% women (25.7-27.9) at baseline. BP was controlled in 1 in 7 subjects with hypertension. At two years, among non-hypertensive adults, average systolic BP increased 2.6mm Hg (95% CI: 2.1-3.1), diastolic BP 0.7mm Hg (95% CI: 0.4-1.0), and 1 in 6 developed hypertension (82.6 per 1000 person years, 95% CI: 80.8-84.4). Risk for developing hypertension was associated with age, low socio-economic status, current alcohol use, overweight, pre-hypertension, and dysglycemia. Risk of incident hypertension was highest (RR=2.95, 95% CI: 2.53-3.45) in individuals with pre-hypertension compared to normal BP. Collectively, 4 modifiable risk factors (pre-hypertension, overweight, dysglycemia, and alcohol use) accounted for 78% of the population attributable risk of incident hypertension.Conclusion: High prevalence and poor control of hypertension, along with high incidence, in South Asian adult population call for urgent preventive measures

Megakaryocytes promote osteoclastogenesis in aging

Megakaryocytes (MKs) support bone formation by stimulating osteoblasts (OBs) and inhibiting osteoclasts (OCs). Aging results in higher bone resorption, leading to bone loss. Whereas previous studies showed the effects of aging on MK-mediated bone formation, the effects of aging on MK-mediated OC formation is poorly understood. Here we examined the effect of thrombopoietin (TPO) and MK-derived conditioned media (CM) from young (3-4 months) and aged (22-25 months) mice on OC precursors. Our findings showed that aging significantly increased OC formation in vitro. Moreover, the expression of the TPO receptor, Mpl, and circulating TPO levels were elevated in the bone marrow cavity. We previously showed that MKs from young mice secrete factors that inhibit OC differentiation. However, rather than inhibiting OC development, we found that MKs from aged mice promote OC formation. Interestingly, these age-related changes in MK functionality were only observed using female MKs, potentially implicating the sex steroid, estrogen, in signaling. Further, RANKL expression was highly elevated in aged MKs suggesting MK-derived RANKL signaling may promote osteoclastogenesis in aging. Taken together, these data suggest that modulation in TPO-Mpl expression in bone marrow and age-related changes in the MK secretome promote osteoclastogenesis to impact skeletal aging

Building a Better Halide Receptor: Optimum Choice of Spacer, Binding Unit, and Halosubstitution

Quantum calculations are used to measure the binding of halides to a number of bipodal dicationic receptors, constructed as a pair of binding units separated by a spacer group. A number of variations are studied. A H atom on each binding unit (imidazolium or triazolium) is replaced by Br or I. Benzene, thiophene, carbazole, and dimethylnaphthalene are considered as spacer groups. Each receptor is paired with halides F-, Cl-, Br-, and I-. I-substitution on the binding unit yields a large enhancement of binding, as much as 13 orders of magnitude; a much smaller increase occurs for bromosubstitution. Imidazolium is a more effective binding agent than is triazolium. Benzene and dimethylnaphthalene represent the best spacers, followed by thiophene and carbazole. F- binds much more strongly than do the other halides which obey the order Cl- \u3e Br- \u3e I-