Simulations of congenital septal defect closure and reactivity testing in patient-specific models of the pediatric pulmonary vasculature: A 3D numerical study with fluid-structure interaction

Clinical imaging methods are highly effective in the diagnosis of vascular pathologies, but they do not currently provide enough detail to shed light on the cause or progression of such diseases, and would be hard pressed to foresee the outcome of surgical interventions. Greater detail of and prediction capabilities for vascular hemodynamics and arterial mechanics are obtained here through the coupling of clinical imaging methods with computational techniques. Three-dimensional, patient-specific geometric reconstructions of the pediatric proximal pulmonary vasculature were obtained from x-ray angiogram images and meshed for use with commercial computational software. Two such models from hypertensive patients, one with multiple septal defects, the other who underwent vascular reactivity testing, were each completed with two sets of suitable fluid and structural initial and boundary conditions and used to obtain detailed transient simulations of artery wall motion and hemodynamics in both clinically measured and predicted configurations. The simulation of septal defect closure, in which input flow and proximal vascular stiffness were decreased, exhibited substantial decreases in proximal velocity, wall shear stress (WSS), and pressure in the post-op state. The simulation of vascular reactivity, in which distal vascular resistance and proximal vascular stiffness were decreased, displayed negligible changes in velocity and WSS but a significant drop in proximal pressure in the reactive state. This new patient-specific technique provides much greater detail regarding the function of the pulmonary circuit than can be obtained with current medical imaging methods alone, and holds promise for enabling surgical planning.     

Effect of zinc supplementation from different sources on growth, nutrient digestibility, blood metabolic profile, and immune response of male guinea pigs

Forty weaned male guinea pigs of 208.20±6.62 g mean body weight were divided into 4 groups of 10 animals in a randomized block design. All of the guinea pigs were fed a basal diet [25% ground maize hay, 30% ground maize grain, 22% ground chickpea (Cicer arietinum L.), 9.5% deoiled rice bran, 6% soybean meal, 6% fish meal, 1.45% mineral supplement (without Zn) and 0.05% ascorbic acid] and available green fodder. Group I served as the control (no Zn supplementation), whereas 20 ppm Zn was added in the diet in groups II, III, and IV either as zinc sulfate (ZnSO₄), zinc amino acid complex (ZAAC), and ZnSO₄ ⁺ ZAAC in equal parts, respectively. Experimental feeding lasted for 70 d, including a 3-d digestibility trial. Blood was collected through cardiac puncture from four animals in each group at d 0 and subsequently at the end of experimental feeding. After 40 d of experimental feeding, four animals from each group were injected with 0.4 mL of Brucella abortus cotton strain-19 vaccine to assess the humoral immune response of the animals. After 10 wk of study, four animals from each group were sacrificed to study the concentration of Zn, Cu, Co, Fe, and Mn in the liver, pancreas and spleen. Results revealed no significant difference in the feed intake, body weight gain, and digestibility of the nutrients, except for crude protein (CP) digestibility, which was significantly (p<0.05) lower in group IV. Although concentrations of serum glucose, Ca, and P and the albumin:globulin (A:G) ratio were similar in the different groups, the total protein, albumin, and serum alkaline phosphatase activity were higher in all of the Zn-supplemented groups on d 70. The serum Zn levels at the end of experimental feeding were significantly higher in groups II and III, whereas serum Mn levels were found to be significantly (p<0.05) higher in groups III and IV. The organ weights (as percentage of body weights) did not show any differences among the treatment groups. Although the Mn concentration was significantly (p<0.05) higher in the pancreas, the Cu concentration was significantly (p<0.05) reduced in the spleen in all of the Zn-supplemented groups. The humoral immune response (antibody titer values) on d 14 of vaccination was significantly (p<0.05) higher in all of the Zn-supplemented groups. It was concluded that the 20-ppm level of Zn in the diet might be adequate for growth and nutrient utilization in guinea pigs, but supplementation of 20-ppm zinc significantly improved the immune response and impact was more prominent with the ZAAC (organic source) compared to ZnSO₄ (inorganic source).     

Unique ayurvedic metallic-herbal preparations, chemical characterization

Bhasmas are unique Ayurvedic metallic preparations with herbal juices/fruits, known in the Indian subcontinent since the seventh century BC and widely recommended for treatment of a variety of chronic ailments. Twenty bhasmas based on calcium, iron, zinc, mercury, silver, potassium, arsenic, copper, tin, and gemstones were analyzed for up to 18 elements by instrumental neutron activation analysis, including their C, H, N, and S contents. In addition to the major constituent element found at % level, several other essential elements such as Na, K, Ca, Mg, V, Mn, Fe, Cu, and Zn have also been found in μg/g amounts and ultratrace (ng/g) amounts of Au and Co. These seem to remain chelated with organic ligands derived from medicinal herbs. The bhasmas are biologically produced nanoparticles and are taken along with milk, butter, honey, or ghee (a preparation from milk), thus, this makes these elements easily assimilable, eliminating their harmful effects and enhancing their biocompatibility. Siddha Makaradhwaja, a mercury preparation is found to be stoichiometrically HgS without any traces of any other element. Similarly, Swet Parpati is stoichiometrically KNO₃ but is found to have Mn, Cu, Zn, Na, P, and Cl as well. An attempt has been made to correlate the metallic contents with their medicinal importance. Na and K, the two electrolytic elements, seem to be well correlated, although K/Na varies in a wide range from 0.06 to 95, with specifically low values for Ca-, Fe-, and Zn-based hasmas. K/P also varies in a wide range from 0.23 to 12, although for most bhasmas (n=12)., it is 2.3±1.2. Further, Fe/Mn is linearly correlated (r=0.96) with Fe in nine noniron bhasmas.     

Light-regulated overexpression of an Arabidopsis phytochrome A gene in rice alters plant architecture and increases grain yield

The phytochromes are a family of red/far-red light absorbing photoreceptors that control plant developmental and metabolic processes in response to changes in the light environment. We report here the overexpression of Arabidopsis thaliana PHYTOCHROME A (PHYA) gene in a commercially important indica rice variety (Oryza sativa L. Pusa Basmati-1). The expression of the transgene was driven by the light-regulated and tissue-specific rice rbcS promoter. Several independent homozygous sixth generation (T₅) transgenic lines were characterized and shown to accumulate relatively high levels of PHYA protein in the light. Under both far-red and red light, PHYA-overexpressing lines showed inhibition of the coleoptile extension in comparison to non-transgenic seedlings. Furthermore, compared with non-transgenic rice plants, mature transgenic plants showed significant reduction in plant height, internode length and internode diameter (including differences in cell size and number), and produced an increased number of panicles per plant. Under greenhouse conditions, rice grain yield was 6–21% higher in three PHYA-overexpressing lines than in non-transgenic plants. These results demonstrate the potential of manipulating light signal-transduction pathways to minimize the problems of lodging in basmati/aromatic rice and to enhance grain productivity.     

Increase in the growth inhibition of bovine pulmonary artery smooth muscle cells by an O-hexanoyl low-molecular-weight heparin derivative

Proliferation of pulmonary artery smooth muscle cells (PASMCs) appears to play a significant role in chronic pulmonary hypertension. The proliferation of PASMCs is strongly inhibited by some commercial heparin preparations. Heparin fragments were prepared by periodate treatment, followed by sodium borohydride reduction, to enhance potency. The tributylammonium salt of this fragmented heparin was O-acylated with hexanoic anhydride. Gradient polyacrylamide gel electrophoresis showed that the major heparin fragment contained eight disaccharide units. NMR analysis showed that approximately one hexanoyl group per disaccharide residue was present. The O-hexanoyl heparin fragments were assayed for growth inhibitory effect on bovine PASMCs in culture. This derivative was found to be more effective in growth inhibition of bovine PASMCs in culture than the heparin from which it was derived. In the future, it is envisioned that this or similar derivatives may be an effective treatment for pulmonary hypertension.     

Comparative QSAR studies on substituted bis-(acridines) and bis-(phenazines)-carboxamides: a new class of anticancer agents

Quantitative structure-activity relationships have been formulated for two sets of DNA binding topoisomerase agents (bis-acridines and bis-phenazines) acting on murine P388 leukemia cells, murine Lewis lung carcinoma (LL(C)) cells and human Jurkat leukemia wild-type (JL(C)) cells. For the acridines, all three QSARs (1-3) show only a (small negative) hydrophobic effect. In sharp contrast, the phenazines in all three studies (4-6) show a strong hydrophobic effect, with the optimum ClogP being near 7.3 for all examples. This suggests that, despite the structural similarity of the compounds, different modes of enzyme and/or DNA binding may be involved.     

Melatonin as a Neuroprotective Agent in the Rodent Models of Parkinson’s Disease: Is it All Set to Irrefutable Clinical Translation?

Parkinson’s disease (PD), a neurodegenerative disorder, is characterized by the selective degeneration of the nigrostriatal dopaminergic neurons, continuing or permanent deficiency of dopamine, accretion of an abnormal form of alpha synuclein in the adjacent neurons, and dysregulation of ubiquitin proteasomal system, mitochondrial metabolism, permeability and integrity, and cellular apoptosis resulting in rigidity, bradykinesia, resting tremor, and postural instability. Melatonin, an indoleamine produced almost in all the organisms, has anti-inflammatory, anti-apoptotic, and anti-oxidant nature. Experimental studies employing 1-methyl 4-phenyl 1, 2, 3, 6-tetrahydropyridine (MPTP), 6-hydroxydopamine (6-OHDA), methamphetamine, rotenone, and maneb and paraquat models have shown an enormous potential of melatonin in amelioration of the symptomatic features of PD. Although a few reviews published previously have described the multifaceted efficacy of melatonin against MPTP and 6-OHDA rodent models, due to development and validation of the newer models as well as the extensive studies on the usage of melatonin in entrenched PD models, it is worthwhile to bring up to date note on the usage of melatonin as a neuroprotective agent in PD. This article presents an update on the usage and applications of melatonin in PD models along with incongruous observations. The impending implications in the clinics, success, limitations, and future prospective have also been discussed in this article.