Mangrove plants as a source of lead compounds for the development of new antiplasmodial drugs from South East coast of India

Malaria is the world's leading killer among the infectious diseases. The treatment of malaria is mystified by the challenges of widespread resistance of the malaria parasites to cheap and affordable antimalarial drugs. The present study was made in an attempt to identify the in vitro antiplasmodial activity against mangrove plant parts. (Avicennia marina, Acanthus ilicifolius, Bruguiera cylindrica, Excoecaria agallocha, Rhizophora apiculata, and Rhizophora mucronata mangrove plant extracts exhibited in vitro antiplasmodial activity against Plasmodium falciparum). Of the selected mangrove plant parts, the bark extract of A. marina exhibited minimum concentration of inhibitory activities IC(50) 49.63 μg.ml(-1). The leaf extract of A. marina, the hypocotyl extract of B. cylindrica, the leaf extract of E. agallocha, the flower extract of R. mucronata, and the hypocotyl extract of R. apiculata showed IC(50) values between 50 and 100 μg.ml(-1). Statistical analysis reveals that significant antiplasmodial activity (P<0.05) was observed between the concentrations and time of exposure. The chemical injury to erythrocytes was also carried out, and it shows that there were no morphological changes in erythrocytes by the ethanolic extract of mangrove plants after 48 h of incubation. The in vitro antiplasmodial activity might be due to the presence of alkaloids, carboxylic acids, coumarins, saponins, flavonoids, xanthoproteins, tannins, phenols, sugars, resins, steroids, and proteins in the ethanolic extracts of mangrove plants. It is concluded from the present study that the ethanolic extracts of mangrove plant parts of A. marina possess lead compounds for the development of antiplasmodial drugs.     

Antiplasmodial activity of two marine polyherbal preparations from <Emphasis Type="Italic">Chaetomorpha antennina</Emphasis> and <Emphasis Type="Italic">Aegiceras corniculatum</Emphasis> against <Emphasis Type="Italic">Plasmodium falciparum</Emphasis>

The ocean covers more than 70% of earth surface and hosts most 300,000 described species of plants and animals to use, which have been virtually unexploited for the development of medicines. Marine plants are the good source of biologically active entities which exhibit therapeutic properties, when applied single or in combination of different plant extracts (polyherbal). Polyherbal preparations are always a complex mixture of different forms and thus different compounds, which might act as agonistic, synergistic, complementary, antagonistic or toxic way. The present study was initially carried out to test the antiplasmodial activity of 13 mangrove plants and eight seaweeds species distributed along the coast of south India. Of these, mangrove species Aegiceras corniculatum and the seaweed species Chaetomorpha antennina have shown maximum antiplasmodial activity. Hence, the present study was mooted out to increase the percentage of antiplasmodial activity when applied as polyherbal preparations. The effect of marine polyherbal preparations from the methanolic extracts of two marine plants A. corniculatum and C. antennina for their antiplasmodial activity was tested. It shows that the polyherbal extract showed 63.50 ± 0.408% suppression of parasitaemia against Plasmodium falciparum at 1.5 mg ml⁻¹ concentration. In vivo test was carried out with rat animal model to find out the effectiveness of the polyherbal extracts in the live system, which reveals that polyherbal extracts have exhibited remarkable antiplasmodial activity (50.57 ± 0.465%) against Plasmodium berghei at 120 mg kg⁻¹ bw. This study shows that combinations of mangrove plants and seaweeds extracts had a source of lead compounds for the development of new drugs for the treatment of malaria.     

Ghrelin attenuates sepsis-induced acute lung injury and mortality in rats

RATIONALE: Our study has shown that plasma levels of ghrelin, a stomach-derived peptide, are significantly reduced in sepsis, and that ghrelin administration improves organ blood flow via a nuclear factor (NF)-kappaB-dependent pathway. However, it remains unknown whether ghrelin has any protective effects on severe sepsis-induced acute lung injury (ALI) and, if so, whether inhibition of NF-kappaB plays any role in it. OBJECTIVES: To test the hypothesis that ghrelin reduces severe sepsis-induced ALI and mortality through inhibition of NF-kappaB. METHODS: Sepsis was induced in rats by cecal ligation and puncture (CLP). Five hours after CLP, a bolus intravenous injection of 2 nmol of ghrelin was followed by continuous infusion of 12 nmol of ghrelin via a minipump for 15 hours. Samples were harvested 20 hours post-CLP (i.e., severe sepsis). Pulmonary levels of ghrelin and proinflammatory cytokines were measured by ELISA. NF-kappaB p65 and IkappaBalpha expression and NF-kappaB activity were measured by Western blot analysis and ELISA, respectively. Pulmonary blood flow was measured with radioactive microspheres. In additional animals, the necrotic cecum was excised 20 hours post-CLP and 10-day survival was recorded. MEASUREMENTS AND MAIN RESULTS: Pulmonary levels of ghrelin decreased significantly 20 hours post-CLP. Ghrelin administration restored pulmonary levels of ghrelin, reduced lung injury, increased pulmonary blood flow, down-regulated proinflammatory cytokines, inhibited NF-kappaB activation, and improved survival in sepsis. Administration of a specific ghrelin receptor antagonist worsened the survival rate after CLP and cecal excision. CONCLUSIONS: Ghrelin can be developed as a novel treatment for severe sepsis-induced ALI. The protective effect of ghrelin is mediated through inhibition of NF-kappaB.     

Fate of retained capsule: a pathognomonic for surgery

Since its introduction in 2001, Wireless Video Capsule enteroscopy is gaining acceptance due to its high diagnostic potential and minimal risk. In some centers, it offers an alternative approach to visualize the small intestine and to evaluate patients with suspected small bowel disease. We present a series of known complications of this procedure and call for a more proactive role in the management of retained capsule.     

Inhibition of Prostate Cancer Cell Colony Formation by the Flavonoid Quercetin Correlates with Modulation of Specific Regulatory Genes

The natural product quercetin is a flavonoid found in many fruits and vegetables. Previous research has shown that quercetin has antitumor, anti-inflammatory, antiallergic, and antiviral activities. In the present investigation we studied the effect of quercetin on the ability of prostate cancer cell lines with various degrees of aggressive potential to form colonies in vitro. Specifically, we examined the molecular mechanisms underlying this effect, including the expression of cell cycle and tumor suppressor genes as well as oncogenes. We observed that quercetin at concentrations of 25 and 50 μM significantly inhibited the growth of the highly aggressive PC-3 prostate cancer cell line and the moderately aggressive DU-145 prostate cancer cell line, whereas it did not affect colony formation by the poorly aggressive LNCaP prostate cancer cell line or the normal fibroblast cell line BG-9. Using the gene array methodology, we found that quercetin significantly inhibited the expression of specific oncogenes and genes controlling G₁, S, G₂, and M phases of the cell cycle. Moreover, quercetin reciprocally up-regulated the expression of several tumor suppressor genes. In conclusion, our results demonstrate that the antitumor effects of quercetin directly correlate with the aggressive potential of prostate cancer cells and that the mechanism(s) of quercetin-mediated antitumor effects may involve up-regulation of tumor suppressor genes and reciprocal down-regulation of oncogenes and cell cycle genes. The results of these studies provide a scientific basis for the potential use of flavonoids as nutraceuticals in the chemoprevention of cancer.     

Inhibition of prostate cancer cell colony formation by the flavonoid quercetin correlates with modulation of specific regulatory genes

The natural product quercetin is a flavonoid found in many fruits and vegetables. Previous research has shown that quercetin has antitumor, anti-inflammatory, antiallergic, and antiviral activities. In the present investigation we studied the effect of quercetin on the ability of prostate cancer cell lines with various degrees of aggressive potential to form colonies in vitro. Specifically, we examined the molecular mechanisms underlying this effect, including the expression of cell cycle and tumor suppressor genes as well as oncogenes. We observed that quercetin at concentrations of 25 and 50 micro M significantly inhibited the growth of the highly aggressive PC-3 prostate cancer cell line and the moderately aggressive DU-145 prostate cancer cell line, whereas it did not affect colony formation by the poorly aggressive LNCaP prostate cancer cell line or the normal fibroblast cell line BG-9. Using the gene array methodology, we found that quercetin significantly inhibited the expression of specific oncogenes and genes controlling G(1), S, G(2), and M phases of the cell cycle. Moreover, quercetin reciprocally up-regulated the expression of several tumor suppressor genes. In conclusion, our results demonstrate that the antitumor effects of quercetin directly correlate with the aggressive potential of prostate cancer cells and that the mechanism(s) of quercetin-mediated antitumor effects may involve up-regulation of tumor suppressor genes and reciprocal down-regulation of oncogenes and cell cycle genes. The results of these studies provide a scientific basis for the potential use of flavonoids as nutraceuticals in the chemoprevention of cancer.     

Anti-beta2 glycoprotein 1 and the anti-phospholipid syndrome

PURPOSE: To describe a patient who presented with bilateral retinal vascular occlusion and the use of anti-beta2 glycoprotein 1 (GPI) antibody testing in the diagnosis of antiphospholipid syndrome. DESIGN: Observational case report. METHODS: Hematological investigations were performed on a 49-year-old man who presented with rapid onset of bilateral severe central retinal vein occlusion. RESULTS: Lupus anticoagulant and anticardiolipin antibody testing was negative. Markedly raised titers of anti-beta2 GPI antibodies were detected on two separate occasions. CONCLUSIONS: The raised titers of anti-beta2 GPI antibodies were considered to strongly suggest an underlying diagnosis of the antiphospholipid syndrome.     

Oxidized low-density lipoprotein and intimal medial thickness in subjects with glucose intolerance: the Chennai Urban Rural Epidemiology Study-25

The aim of the present study was to assess the association of oxidized low-density lipoprotein (OX-LDL) with carotid intimal medial thickness (IMT) in different grades of glucose intolerance in Asian Indians. Three groups were recruited from the Chennai Urban Rural Epidemiology Study, a population-based study: group 1, normal glucose tolerance (NGT) (n = 175); group 2, impaired glucose tolerance (IGT) (n = 175); and group 3, type 2 diabetes mellitus (n = 175). Oxidized LDL (enzyme-linked immunosorbent assay) and carotid IMT (high-resolution B-mode ultrasonography) were assessed. Subjects with diabetes had higher IMT values (0.85 +/- 0.30 mm) compared with those who have IGT (0.79 +/- 0.16 mm, P < .05) and NGT (0.71 +/- 0.12 mm, P < .001). Subjects with diabetes (40.1 +/- 13.1 U/L) and IGT (34.3 +/- 12.8 U/L) had significantly higher mean OX-LDL values compared with the NGT group (26.2 +/- 16.6 U/L, P < .001). Oxidized LDL showed a correlation with IMT (total population: r = 0.294, P < .001; subjects with NGT: r = 0.444, P < .001; and subjects with IGT: r = 0.481, P < .001). In multiple linear regression analysis, OX-LDL showed a strong association with IMT (beta = .005, P < .001), even after adjusting for age, sex (beta = .003, P < .001), and glucose intolerance (beta = .002, P < .001). In conclusion, OX-LDL levels increase with increasing glucose intolerance. Oxidized LDL is associated with carotid IMT and this is independent of age, sex, and glucose intolerance status.     

Computed tomographic angiography in tetralogy of Fallot

Echocardiography is often inadequate for imaging tetralogy of Fallot, prompting cineangiography. This study prospectively evaluated multidetector computed tomographic angiography for preoperative evaluation of tetralogy of Fallot in 112 consecutive patients. Forty-eight had nonconfluent or hypoplastic pulmonary arteries (mean z-score, -2; range, -11.1-0.13) permitting only palliative or no surgery; 64 had adequate pulmonary artery anatomy (mean z-score, 0.59; range, -2.53-3.4) allowing total repair. The surgical data of 50 patients who underwent total correction were compared with transthoracic echocardiography and multidetector computed tomographic angiography findings. Multidetector computed tomographic angiography tended to reveal unsuspected collaterals and coronary abnormalities besides outlining the right ventricular outflow tract and pulmonary artery branches. The branch pulmonary artery diameter z-score was the most important determinant of surgical strategy, with the worst figures being associated with no surgical options or palliative surgery, and the best figures leading to corrective surgery. The mean radiation dose was 3.45 mSv. Multidetector computed tomographic angiography is a powerful supplement to echocardiography in the preoperative evaluation of tetralogy of Fallot.     

Chloroquine sensitizes biofilms of Candida albicans to antifungal azoles

Biofilms formed by Candida albicans, a human pathogen, are known to be resistant to different antifungal agents. Novel strategies to combat the biofilm associated Candida infections like multiple drug therapy are being explored. In this study, potential of chloroquine to be a partner drug in combination with four antifungal agents, namely fluconazole, voriconazole, amphotericin B, and caspofungin, was explored against biofilms of C. albicans. Activity of various concentrations of chloroquine in combination with a particular antifungal drug was analyzed in a checkerboard format. Growth of biofilm in presence of drugs was analyzed by XTT-assay, in terms of relative metabolic activity compared to that of drug free control. Results obtained by XTT-metabolic assay were confirmed by scanning electron microscopy. The interactions between chloroquine and four antifungal drugs were determined by calculating fractional inhibitory concentration indices. Azole resistance in biofilms was reverted significantly (p < 0.05) in presence of 250 μg/mL of chloroquine, which resulted in inhibition of biofilms at very low concentrations of antifungal drugs. No significant alteration in the sensitivity of biofilms to caspofungin and amphotericin B was evident in combination with chloroquine. This study for the first time indicates that chloroquine potentiates anti-biofilm activity of fluconazole and voriconazole.