Amalaki rasayana, a traditional Indian drug enhances cardiac mitochondrial and contractile functions and improves cardiac function in rats with hypertrophy.

We evaluated the cardioprotective effect of Amalaki Rasayana (AR), a rejuvenating Ayurvedic drug prepared from Phyllanthus emblica fruits in the reversal of remodeling changes in pressure overload left ventricular cardiac hypertrophy (LVH) and age-associated cardiac dysfunction in male Wistar rats. Six groups (aging groups) of 3 months old animals were given either AR or ghee and honey (GH) orally; seventh group was untreated. Ascending aorta was constricted using titanium clips in 3 months old rats (N = 24; AC groups) and after 6 months, AR or GH was given for further 12 months to two groups; one group was untreated. Histology, gene and protein expression analysis were done in heart tissues. Chemical composition of AR was analyzed by HPLC, HPTLC and LC-MS. AR intake improved (P < 0.05) cardiac function in aging rats and decreased LVH (P < 0.05) in AC rats as well as increased (P < 0.05) fatigue time in treadmill exercise in both groups. In heart tissues of AR administered rats of both the groups, SERCA2, CaM, Myh11, antioxidant, autophagy, oxidative phosphorylation and TCA cycle proteins were up regulated. ADRB1/2 and pCREB expression were increased; pAMPK, NF-kB were decreased. AR has thus a beneficial effect on myocardial energetics, muscle contractile function and exercise tolerance capacity.

Arterialization and anomalous vein wall remodeling in varicose veins is associated with upregulated FoxC2-Dll4 pathway.

Varicose veins of lower extremities are a heritable common disorder. Mechanisms underlying its pathogenesis are still vague. Structural failures such as valve weakness and wall dilatation in saphenous vein result in venous retrograde flow in lower extremities of body. Reflux of blood leads to distal high venous pressure resulting in distended veins. In an earlier study, we observed a positive association between c.-512C>T FoxC2 gene polymorphism and upregulated FoxC2 expression in varicose vein specimens. FoxC2 overexpression in vitro in venous endothelial cells resulted in the elevated mRNA expression of arterial endothelial markers such as Delta-like ligand 4 (Dll4) and Hairy/enhancer-of-split related with YRPW motif protein 2 (Hey2). We hypothesized that an altered FoxC2-Dll4 signaling underlies saphenous vein wall remodeling in patients with varicose veins. Saphenous veins specimens were collected from 22 patients with varicose veins and 20 control subjects who underwent coronary artery bypass grafting. Tissues were processed for paraffin embedding and sections were immunostained for Dll4, Hey2, EphrinB2, α-SMA, Vimentin, and CD31 antigens and examined under microscope. These observations were confirmed by quantitative real-time PCR and western blot analysis. An examination of varicose vein tissue specimens by immunohistochemistry indicated an elevated expression of Notch pathway components, such as Dll4, Hey2, and EphrinB2, and smooth muscle markers, which was further confirmed by gene and protein expression analyses. We conclude that the molecular alterations in Dll4-Hey2 signaling are associated with smooth muscle cell hypertrophy and hyperplasia in varicose veins. Our observations substantiate a significant role for altered FoxC2-Dll4 signaling in structural alterations of saphenous veins in patients with varicose veins.

Drug Resistance of Endocardial Endothelial Cells is Related to Higher Endogenous ABCG2.

Endocardial endothelial cells (EECs), when compared with endothelial cells of arteries and veins, possess higher resistance to apoptosis-inducing anticancer agents. The mechanism of this resistance property is unknown. We have investigated the molecular mechanism, which contributes to increased cell survival capacity in EECs. We explored whether the resistance to apoptosis is associated with the cellular expression of ATP-binding cassette transporters such as P-glycoprotein, MRP-1, and ABCG2. We used primary and immortalized porcine endocardial endothelial cells (PEECs and hTERT PEECs) and compared the results with that in porcine aortic endothelial cells (PAECs), left atrioventricular valve endothelial cells (PVECs), and human umbilical vein endothelial cell line (EA.hy926). FACS and immunoblot analysis revealed a significantly higher expression of ABCG2 in PEECs and hTERT PEECs compared to PAECs, PVECs, and EA.hy926. Using apoptosis-inducing anticancer agents such as doxorubicin and camptothecin, through chromatin condensation assay and immunoblot analysis, we demonstrated a higher resistance to apoptosis in EECs compared to PAECs, PVECs, and EA.hy926. Interestingly, resistance in EECs reversed in presence of ABCG2 specific inhibitor, fumitremorgin C. Our observations suggest that an inherently high expression of ABCG2 in EECs protects them against apoptosis in presence of anticancer agents.

Cationic, amphiphilic dextran nanomicellar clusters as an excipient for dry powder inhaler formulation.

Effective delivery of drugs to alveoli in a controlled manner using hydrophobic polymers as carriers has already been reported. Preclinical studies revealed that toxicity and hydrophobicity are related to each other in pulmonary delivery. Here, we are reporting a chemically modified dextran having amphiphilicity and cationicity achieved by controlled grafting of stearyl amine. Two proportions of lipopolymers were synthesized and physico-chemical characterization was carried out. In vivo evaluation of sub-acute toxicity of the synthesized lipopolymer in Sprague-Dawley rats was carried out for three months. This was followed by a histological evaluation of the sacrificed animal's lung. Further, the synthesized lipopolymer was formulated with drug (Rifampicin) loaded inhalable microparticles through spray drying. The final drug formulation was tested for toxicity and proinflammatory responses in human cell lines. Dose deposition efficiency of the formulation was determined using Anderson Cascade Impactor.

In vitro antioxidant activities of the methanol extract and its different solvent fractions obtained from the fruit pericarp of Terminalia bellerica.

Terminalia bellerica has been used as a traditional medicine in a variety of ailments including anaemia, asthma, cancer, inflammation, rheumatism and hypertension. In this study, the free radical scavenging and antioxidant activities of methanol extract (ME) and its different solvent fractions (namely hexane (HE), ethyl acetate (EA), butanol (BL) and water (WA)) of the T. bellerica fruit pericarp were evaluated and compared with standard antioxidant compounds like gallic acid (GA), catechin and ascorbic acid. Among the different fractions tested, the EA fraction exhibited higher antioxidant and radical scavenging activity against 1,1-diphenyl-2-picrylhydrazyl (DPPH), superoxide and hydroxyl radicals than the other fractions, which may be attributed to its higher phenolic and flavonoid content, since a linear relation was observed between the phenolic content and the antioxidant parameters. The HPTLC analysis of the EA fraction revealed that it mainly contains GA and ferulic acid (FA) as major phenolics, and the higher antioxidant activities of EA fraction may be due to the presence of these compounds.

Estimation of fungal growth using the ergosterol assay: a rapid tool in assessing the microbiological status of grains and feeds.

AIM: To use ergosterol assay as a rapid tool to assess the extent of fungal contamination in grains and feeds. METHODS AND RESULTS: Ergosterol was extracted from moulds and quantified using a modified method based on Seitz et al. (1977). A good correlation coefficient of 0.9998 was obtained for ergosterol standards and a strong correlation (R(2) = 0 x 9645) was established between the ergosterol content and the growth of Aspergillus niger ATCC 24126. This shows that this assay can be used to estimate fungal growth. The ergosterol contents and amount of carbon dioxide produced in both Control and Myco CURB (brand) liquid-treated corns were measured over 36 days. Ergosterol contents of pelleted pig feeds were also determined. In both experiments, the levels of ergosterol in the control samples were significantly higher than those of the mould-inhibitor-treated samples. CONCLUSIONS: A strong positive correlation (Spearman, Rs = 0 x 7241) was observed between the ergosterol content and the degree of fungal growth. Hence, ergosterol assay can be used as a rapid tool to assess the microbiological status of grains and feeds. SIGNIFICANCE AND IMPACT OF THE STUDY: This study affirms that ergosterol assay is a rapid and accurate tool that can be used for the assessment of the feed quality.

Spent ion exchange resin-its treatment from the point of view of safe disposal.

Ion exchange process is one of the treatment methods for radioactive waste. The resin becomes no longer useful after number of cycles of usage. At the same time the regenerated resin cannot be considered as non active waste for disposal. Hence it is felt necessary that the regenerated resin is treated in a fashion so as to result in a form which can be considered as inactive material. It is possible to convert this spent resin into multivalent ionic form which are generally non leachable, thus providing the necessary properties for meeting the disposal criteria. Studies were carried out for the exchange of radioactive ions on these resins with ions like Al3+, Sn4+, Pb2+ and Fe3+ etc. The studies included leachability aspects, exchange with other active ions, thermal characteristics, compressive strength of the cement blocks loaded with the resin etc. Our studies indicated that the order of the stability of the resin with respect to properties like leachability, exchange properties etc. follow the trend as follows: Sn4+ > Pb2+ > Al3+ > Fe3+.

Photochemistry of arylidene-beta-ionones: a highly efficient route to novel tricyclic ketones through intramolecular, exoselective photochemical (4 + 2) cycloadditions, occurring only in an aqueous-organic solvent.

(E,E)-Arylidene-beta-ionones (1a-f) are converted to 1,7,7-trimethyl-3-(E-2'-arylethenyl)-2-oxabicyclo[4.4.0]deca-3,5-dienes (3a-f, approximately 90%) by irradiating in anhydrous solvents. Irradiation of (3a-f) in aqueous methanol results in Z,E-arylidene-beta-ionones (2), through retro-electrocyclization, which undergoes an intramolecular, exo-selective [4 + 2] photocycloaddition leading to 11-(exo)-aryl-1,7,7-trimethyl-tricyclo[4.4.0.1(2,4)]undec-5-ene-3-ones (8a-f, 60-80%). The latter rearrange over silica gel to afford, quantitatively, 5-aryl-7,11,11-trimethyl-tricyclo[5.4.0.0(3,6)]undec-1-ene-4-ones (5a-f). Irradiation of 1a-f in aqueous methanol leads to 8a-f, except in case of 1c,f wherein formation, respectively, of tricyclic ketones 9c (55%) and 9f (80%), derived from photodeconjugation in 2, followed by intramolecular [4 + 2] cycloaddition, is observed.

Modulation of feeding and drinking behaviour by catecholamines injected into nucleus caudatus in rats.

Lesions of nucleus caudatus have been documented to produce adipsia and aphasia in rats. Injection of dopamine into this nucleus has been shown to facilitate water intake in rats. But, reports are not available on the effects of intracerebral injection of epinephrine and norepinephrine on feeding and drinking behaviour in animal models. Therefore, in the present study the effect of adrenaline and noradrenaline injected into nucleus caudatus on food and water intake in rats was assessed. 24 h basal food and water intakes were recorded in Wistar rats and were found to be 12.37 +/- 0.20 g and 22.04 +/- 0.27 ml respectively. Stainless steel cannulae were implanted stereotaxically into the nucleus caudatus. Four different doses (0.1 microgram, 0.5 microgram, 1 microgram, and 2 micrograms) of adrenaline and noradrenaline were injected into the nucleus caudatus through the implanted cannulae in separate groups of animals and their 24 h food and water intakes were recorded following these injections. No change in food and water intake was observed following the administration of different doses of adrenaline. A significant increase in 24 h food intake reaching a maximum of 16.03 +/- 0.15 g at 2 micrograms dose, without change in water intake was observed following administration of different doses of noradrenaline. The noradrenaline-facilitated food intake was blocked when noradrenaline was injected following injection of phentolamine, an alpha-receptor blocker. The bilateral lesions of nucleus caudatus resulted in a significant and sustained inhibition of food (8.98 +/- 0.17 g) and water intake (19.12 +/- 0.16 ml). These observations suggest that nucleus caudatus is involved in regulation of food and water intakes in rats. Noradrenaline-facilitated food intake is mediated by alpha-receptors. Adrenaline does not affect these ingestive behaviours when injected into the nucleus caudatus in rats.

Modulation of feeding and drinking behaviour by catecholamines injected into nucleus accumbens in rats.

Nucleus accumbens is proposed as one of the centers in the neural circuitry involved in the regulation of feeding and drinking behaviour in rats. Injection of dopamine and angiotensin-II into this nucleus has been documented to affect water and food intake in rats. Reports on the effect of intracerebral injection of catecholamines on feeding and drinking behaviour in animal models are conflicting. Therefore, in the present study the effect of adrenaline and noradrenaline injected into nucleus accumbens on food and water intake in rats was assessed. 24 h basal food and water intakes were recorded in Wistar rats and were found to be 12.3 +/- 0.46 g and 21.7 +/- 1.03 ml respectively. Stainless steel cannulae were implanted stereotaxically into the nucleus accumbens. Four different doses (0.1 microgram, 0.5 microgram, 1 microgram, and 2 micrograms) of adrenaline and noradrenaline were injected into the nucleus accumbens through the implanted cannulae in different group of animals and their 24 h food and water intakes were recorded following these injections. No change in food and water intake was observed following the administration of different doses of adrenaline. A significant increase in 24 h water intake reaching a maximum of 28.88 +/- 1.45 ml at 1 microgram dose, without change in food intake was observed following administration of different doses of noradrenaline. The noradrenaline-facilitated water intake was blocked when noradrenaline was injected following injection of phentolamine, an alpha-receptor blocker. The bilateral lesions of nucleus accumbens resulted in a significant and sustained inhibition of water intake (16.61 +/- 0.67 ml) without change in food intake. These observations suggest that noradrenaline facilitates water intake without affecting food intake when injected into the nucleus accumbens in rats and the dipsogenic effect of noradrenaline is mediated by alpha-receptors. Adrenaline does not affect these ingestive behaviours when injected into the nucleus accumbens in rats.

Pilonidal sinus of the nose.

We report an unusual case of a pilonidal sinus appearing on the nose. From the clinical and pathological findings, we find it difficult to believe that it is an acquired condition. En bloc excision by an external rhinoplasty approach was performed with no evidence of any recurrence.